16-56870675-C-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 4P and 20B. PM1PM5BP4_StrongBP6_Very_StrongBA1
The ENST00000563236.6(SLC12A3):āc.791C>Gā(p.Ala264Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,613,832 control chromosomes in the GnomAD database, including 758,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A264D) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000563236.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC12A3 | NM_001126108.2 | c.791C>G | p.Ala264Gly | missense_variant | 6/26 | ENST00000563236.6 | NP_001119580.2 | |
SLC12A3 | NM_000339.3 | c.791C>G | p.Ala264Gly | missense_variant | 6/26 | NP_000330.3 | ||
SLC12A3 | NM_001126107.2 | c.788C>G | p.Ala263Gly | missense_variant | 6/26 | NP_001119579.2 | ||
SLC12A3 | NM_001410896.1 | c.788C>G | p.Ala263Gly | missense_variant | 6/26 | NP_001397825.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC12A3 | ENST00000563236.6 | c.791C>G | p.Ala264Gly | missense_variant | 6/26 | 1 | NM_001126108.2 | ENSP00000456149 | A1 | |
SLC12A3 | ENST00000438926.6 | c.791C>G | p.Ala264Gly | missense_variant | 6/26 | 1 | ENSP00000402152 | A1 | ||
SLC12A3 | ENST00000566786.5 | c.788C>G | p.Ala263Gly | missense_variant | 6/26 | 1 | ENSP00000457552 | P4 | ||
SLC12A3 | ENST00000262502.5 | c.788C>G | p.Ala263Gly | missense_variant | 6/26 | 5 | ENSP00000262502 | A1 |
Frequencies
GnomAD3 genomes AF: 0.979 AC: 148873AN: 152110Hom.: 72869 Cov.: 30
GnomAD3 exomes AF: 0.978 AC: 245970AN: 251456Hom.: 120339 AF XY: 0.978 AC XY: 132883AN XY: 135912
GnomAD4 exome AF: 0.968 AC: 1414989AN: 1461604Hom.: 685115 Cov.: 44 AF XY: 0.969 AC XY: 704391AN XY: 727142
GnomAD4 genome AF: 0.979 AC: 148991AN: 152228Hom.: 72928 Cov.: 30 AF XY: 0.979 AC XY: 72886AN XY: 74418
ClinVar
Submissions by phenotype
Familial hypokalemia-hypomagnesemia Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 21, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 17, 2016 | This is a RefSeq error. The reference base (c.791C) is the minor allele. This al lele (C) has been identified in 3.65% (2438/66728) of European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs15 29927) and thus meets criteria to be classified as benign. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2019 | This variant is associated with the following publications: (PMID: 25892104, 17460608, 10988270, 15480096, 27884173, 11940055, 20981092, 14766743, 21415153, 22245519) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at