rs374337406
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005198.5(CHKB):c.1006G>A(p.Glu336Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E336D) has been classified as Uncertain significance.
Frequency
Consequence
NM_005198.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHKB | NM_005198.5 | c.1006G>A | p.Glu336Lys | missense_variant | 9/11 | ENST00000406938.3 | |
CHKB-CPT1B | NR_027928.2 | n.1224G>A | non_coding_transcript_exon_variant | 9/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHKB | ENST00000406938.3 | c.1006G>A | p.Glu336Lys | missense_variant | 9/11 | 1 | NM_005198.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249008Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134802
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461808Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727202
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74342
ClinVar
Submissions by phenotype
Megaconial type congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 336 of the CHKB protein (p.Glu336Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 577497). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at