NM_019023.5(PRMT7):c.1159A>G (p.Arg387Gly) AND Short stature-brachydactyly-obesity-global developmental delay syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jul 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000256485.4

Allele description [Variation Report for NM_019023.5(PRMT7):c.1159A>G (p.Arg387Gly)]

NM_019023.5(PRMT7):c.1159A>G (p.Arg387Gly)

Gene:

PRMT7:protein arginine methyltransferase 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_019023.5(PRMT7):c.1159A>G (p.Arg387Gly)

HGVS:

NC_000016.10:g.68346248A>G
NG_054896.1:g.40275A>G
NM_001184824.4:c.1009A>G
NM_001290018.2:c.1159A>G
NM_001351143.3:c.1159A>G
NM_001351144.3:c.1159A>G
NM_001378018.1:c.1159A>G
NM_001378020.1:c.952A>G
NM_001378021.1:c.922A>G
NM_001378022.1:c.922A>G
NM_001378023.1:c.922A>G
NM_019023.3:c.1159A>G
NM_019023.5:c.1159A>GMANE SELECT
NP_001171753.1:p.Arg337Gly
NP_001276947.1:p.Arg387Gly
NP_001338072.1:p.Arg387Gly
NP_001338073.1:p.Arg387Gly
NP_001364947.1:p.Arg387Gly
NP_001364949.1:p.Arg318Gly
NP_001364950.1:p.Arg308Gly
NP_001364951.1:p.Arg308Gly
NP_001364952.1:p.Arg308Gly
NP_061896.1:p.Arg387Gly
NC_000016.9:g.68380151A>G
NM_019023.2:c.1159A>G
NR_147056.3:n.1323A>G
NR_147057.3:n.1458A>G
NR_147058.3:n.1458A>G
NR_165365.1:n.1458A>G
NR_165366.1:n.1323A>G
NR_165367.1:n.1323A>G
NR_165368.1:n.1421A>G
NR_165369.1:n.1286A>G
NR_165370.1:n.1286A>G
NR_165371.1:n.1349A>G
NR_165372.1:n.1458A>G
NR_165373.1:n.1421A>G
Q9NVM4:p.Arg387Gly

Protein change:

R308G; ARG387GLY

Links:

UniProtKB: Q9NVM4#VAR_076330; OMIM: 610087.0004; dbSNP: rs762515973

NCBI 1000 Genomes Browser:

rs762515973

Molecular consequence:

NM_001184824.4:c.1009A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001290018.2:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351143.3:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351144.3:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378018.1:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378020.1:c.952A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378021.1:c.922A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378022.1:c.922A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378023.1:c.922A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_019023.5:c.1159A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_147056.3:n.1323A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147057.3:n.1458A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_147058.3:n.1458A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165365.1:n.1458A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165366.1:n.1323A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165367.1:n.1323A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165368.1:n.1421A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165369.1:n.1286A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165370.1:n.1286A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165371.1:n.1349A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165372.1:n.1458A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165373.1:n.1421A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Short stature-brachydactyly-obesity-global developmental delay syndrome
Synonyms:: Short stature, brachydactyly, intellectual developmental disability, and seizures; SHORT STATURE, BRACHYDACTYLY, IMPAIRED INTELLECTUAL DEVELOPMENT, AND SEIZURES
Identifiers:: MONDO: MONDO:0014944; MedGen: C4310689; OMIM: 617157

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C-terminal-binding protein 1 isoform X1 [Polypterus senegalus]
C-terminal-binding protein 1 isoform X1 [Polypterus senegalus]
gi|1993921103|ref|XP_039630636.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000323184	OMIM	no assertion criteria provided	Pathogenic (Jul 3, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV005087109	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26437029, 29453417, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000323184

OMIM

no assertion criteria provided

Pathogenic
(Jul 3, 2020)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV005087109

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Akawi N, McRae J, Ansari M, Balasubramanian M, Blyth M, Brady AF, Clayton S, Cole T, Deshpande C, Fitzgerald TW, Foulds N, Francis R, Gabriel G, Gerety SS, Goodship J, Hobson E, Jones WD, Joss S, King D, Klena N, Kumar A, Lees M, et al.

Nat Genet. 2015 Nov;47(11):1363-9. doi: 10.1038/ng.3410. Epub 2015 Oct 5.

PubMed [citation]

PMID:: 26437029
PMCID:: PMC5988033

Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders.

Dillon OJ, Lunke S, Stark Z, Yeung A, Thorne N; Melbourne Genomics Health Alliance., Gaff C, White SM, Tan TY.

Eur J Hum Genet. 2018 May;26(5):644-651. doi: 10.1038/s41431-018-0099-1. Epub 2018 Feb 16.

PubMed [citation]

PMID:: 29453417
PMCID:: PMC5945679

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000323184.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the c.1159A-G transition (c.1159A-G, NM_019023.2) in the PRMT7 gene, resulting in an arg387-to-gly (R387G) substitution that was found in compound heterozygous state in a woman with short stature, brachydactyly, impaired intellectual development, and seizures (SBIDDS; 617157) by Akawi et al. (2015), see 610087.0003.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005087109.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with short stature, brachydactyly, intellectual developmental disability, and seizures (MIM#617157). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glycine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (12 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been observed as compound heterozygous in two individuals with syndromic developmental delay or syndromic intellectual disability with seizures (PMID: 26437029, 29453417). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1201 - Heterozygous variant detected in trans with a second pathogenic heterozygous variant, p.(Gly560Lysfs*22), in a recessive disease. (SP) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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