NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 7, 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:: RCV003317513.1

Allele description [Variation Report for NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)]

NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)

Gene:

C19orf12:chromosome 19 open reading frame 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q12

Genomic location:

Preferred name:

NM_031448.6(C19orf12):c.161G>C (p.Gly54Ala)

HGVS:

NC_000019.10:g.29702977C>G
NG_031970.2:g.17813G>C
NM_001031726.4:c.161G>C
NM_001256046.3:c.161G>C
NM_001256047.2:c.161G>C
NM_001282929.1:c.-32G>C
NM_001282930.3:c.-32G>C
NM_001282931.3:c.-32G>C
NM_031448.6:c.161G>CMANE SELECT
NP_001026896.3:p.Gly54Ala
NP_001242975.1:p.Gly54Ala
NP_001242976.1:p.Gly54Ala
NP_113636.2:p.Gly54Ala
NC_000019.9:g.30193884C>G
NM_001031726.3:c.194G>C

Protein change:

G54A

Links:

dbSNP: rs752450983

NCBI 1000 Genomes Browser:

rs752450983

Molecular consequence:

NM_001282929.1:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001282930.3:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001282931.3:c.-32G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001031726.4:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001256046.3:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001256047.2:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_031448.6:c.161G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004020762	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 7, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004020762

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 7, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004020762.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: C19orf12 c.161G>C (p.Gly54Ala) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. c.161G>C affects the first base pair of Exon 3 and could affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.2e-05 in 249090 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in C19orf12 causing Neurodegeneration With Brain Iron Accumulation (7.2e-05 vs 0.0006), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.161G>C in individuals affected with Neurodegeneration With Brain Iron Accumulation and no experimental evidence demonstrating its impact on protein function have been reported. Two other variants affecting the same base pair have been associated with pathogenicity in ClinVar (c.161G>A (p.Gly54Glu) and c.161G>T (p.Gly54Val)), however enough evidence is not available at this time to determine role of this variant in disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Sep 29, 2024

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Relating variation to medicine