7-143330817-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM5BP4_StrongBP6BS2
The NM_000083.3(CLCN1):c.899G>A(p.Arg300Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,162 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R300W) has been classified as Pathogenic.
Frequency
Consequence
NM_000083.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00459 AC: 698AN: 152168Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00475 AC: 1195AN: 251402Hom.: 5 AF XY: 0.00498 AC XY: 677AN XY: 135866
GnomAD4 exome AF: 0.00734 AC: 10728AN: 1461876Hom.: 45 Cov.: 32 AF XY: 0.00729 AC XY: 5303AN XY: 727238
GnomAD4 genome AF: 0.00458 AC: 698AN: 152286Hom.: 1 Cov.: 32 AF XY: 0.00422 AC XY: 314AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:5
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:3
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CLCN1: PP3, BS2 -
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Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:2
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The c.899G>A (p.(Arg300Gln)) variant was found in a heterozygous state in 2 Slovak patients with Myotonia congenita: the first one carried another 2 Likely Pathogenic variants: c.1231G>T and C2680C>T; while in the second one, no other Pathogenic or Likely pathogenic variants were found. GnomAD Exomes Version: 4.0 indicates the frequency of f = 0.00734. This variant has been reported in HGMD database CM940284. -
Congenital myotonia, autosomal recessive form Uncertain:1
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Batten-Turner congenital myopathy Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at