NM_000492.4(CFTR):c.1115A>G (p.Gln372Arg) AND Cystic fibrosis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003507371.3

Allele description [Variation Report for NM_000492.4(CFTR):c.1115A>G (p.Gln372Arg)]

NM_000492.4(CFTR):c.1115A>G (p.Gln372Arg)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1115A>G (p.Gln372Arg)

HGVS:

NC_000007.14:g.117540345A>G
NG_016465.4:g.79562A>G
NM_000492.4:c.1115A>GMANE SELECT
NP_000483.3:p.Gln372Arg
LRG_663:g.79562A>G
NC_000007.13:g.117180399A>G
NM_000492.3:c.1115A>G

Protein change:

Q372R

Links:

dbSNP: rs1799033866

NCBI 1000 Genomes Browser:

rs1799033866

Molecular consequence:

NM_000492.4:c.1115A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: Mucoviscidosis
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004270972	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32777524, 28492532
SCV005035620	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004270972

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 25, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005035620

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 8, 2023)

germline

clinical testing

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

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients.

Luo S, Feng J, Zhang Y, Yang X, Ma G, Hu T, Xi Y, Tu X, Wang C, Zhang H, Zou Z, Zhang Y.

Gene. 2021 Jan 10;765:145045. doi: 10.1016/j.gene.2020.145045. Epub 2020 Aug 8.

PubMed [citation]

PMID:: 32777524

Details of each submission

From Invitae, SCV004270972.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 994320). This missense change has been observed in individual(s) with congenital absence of the vas deferens (PMID: 32777524). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 372 of the CFTR protein (p.Gln372Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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

From Ambry Genetics, SCV005035620.1

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

Description

The p.Q372R variant (also known as c.1115A>G), located in coding exon 8 of the CFTR gene, results from an A to G substitution at nucleotide position 1115. The glutamine at codon 372 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with congenital absence of the vas deferens (Luo S et al. Gene, 2021 Jan;765:145045). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 16, 2024

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