rs149747266
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_133642.5(LARGE1):c.941A>T(p.Gln314Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,052 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. Q314E) has been classified as Uncertain significance.
Frequency
Consequence
NM_133642.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LARGE1 | NM_133642.5 | c.941A>T | p.Gln314Leu | missense_variant | 8/15 | ENST00000397394.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARGE1 | ENST00000397394.8 | c.941A>T | p.Gln314Leu | missense_variant | 8/15 | 5 | NM_133642.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251426Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135890
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727228
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 30, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 11, 2022 | - - |
Muscular dystrophy-dystroglycanopathy type B6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 314 of the LARGE1 protein (p.Gln314Leu). This variant is present in population databases (rs149747266, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 586123). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 05, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at