rs376968555
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The ENST00000371589.9(MAN1B1):c.1742G>A(p.Gly581Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,446 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000371589.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAN1B1 | NM_016219.5 | c.1742G>A | p.Gly581Asp | missense_variant | 11/13 | ENST00000371589.9 | NP_057303.2 | |
MAN1B1 | XM_006716945.5 | c.1742G>A | p.Gly581Asp | missense_variant | 11/12 | XP_006717008.1 | ||
MAN1B1 | NR_045720.2 | n.1732G>A | non_coding_transcript_exon_variant | 11/13 | ||||
MAN1B1 | NR_045721.2 | n.1888G>A | non_coding_transcript_exon_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAN1B1 | ENST00000371589.9 | c.1742G>A | p.Gly581Asp | missense_variant | 11/13 | 1 | NM_016219.5 | ENSP00000360645 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152234Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000187 AC: 47AN: 251188Hom.: 2 AF XY: 0.000177 AC XY: 24AN XY: 135866
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461094Hom.: 8 Cov.: 31 AF XY: 0.000121 AC XY: 88AN XY: 726868
GnomAD4 genome AF: 0.000131 AC: 20AN: 152352Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9AN XY: 74492
ClinVar
Submissions by phenotype
Rafiq syndrome Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | MAN1B1: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at