rs34292743
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_133642.5(LARGE1):c.1548C>T(p.Tyr516=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,614,248 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 137 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 123 hom. )
Consequence
LARGE1
NM_133642.5 synonymous
NM_133642.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.64
Genes affected
LARGE1 (HGNC:6511): (LARGE xylosyl- and glucuronyltransferase 1) This gene encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. The protein encoded by this gene is the glycotransferase that adds the final xylose and glucuronic acid to alpha-dystroglycan and thereby allows alpha-dystroglycan to bind ligands including laminin 211 and neurexin. Mutations in this gene cause several forms of congenital muscular dystrophy characterized by cognitive disability and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 22-33304411-G-A is Benign according to our data. Variant chr22-33304411-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 95166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-33304411-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.64 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0817 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LARGE1 | NM_133642.5 | c.1548C>T | p.Tyr516= | synonymous_variant | 12/15 | ENST00000397394.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LARGE1 | ENST00000397394.8 | c.1548C>T | p.Tyr516= | synonymous_variant | 12/15 | 5 | NM_133642.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0240 AC: 3660AN: 152254Hom.: 135 Cov.: 33
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GnomAD3 exomes AF: 0.00637 AC: 1600AN: 251318Hom.: 66 AF XY: 0.00481 AC XY: 654AN XY: 135830
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GnomAD4 exome AF: 0.00249 AC: 3636AN: 1461876Hom.: 123 Cov.: 32 AF XY: 0.00219 AC XY: 1593AN XY: 727240
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GnomAD4 genome ? AF: 0.0240 AC: 3662AN: 152372Hom.: 137 Cov.: 33 AF XY: 0.0230 AC XY: 1717AN XY: 74524
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 17, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2014 | 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. - |
Muscular dystrophy-dystroglycanopathy type B6 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 04, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 26, 2018 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at