rs373430024
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016219.5(MAN1B1):c.586C>T(p.Arg196Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R196H) has been classified as Likely benign.
Frequency
Consequence
NM_016219.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAN1B1 | NM_016219.5 | c.586C>T | p.Arg196Cys | missense_variant | 4/13 | ENST00000371589.9 | |
MAN1B1 | XM_006716945.5 | c.586C>T | p.Arg196Cys | missense_variant | 4/12 | ||
MAN1B1 | NR_045720.2 | n.601C>T | non_coding_transcript_exon_variant | 4/13 | |||
MAN1B1 | NR_045721.2 | n.732C>T | non_coding_transcript_exon_variant | 5/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAN1B1 | ENST00000371589.9 | c.586C>T | p.Arg196Cys | missense_variant | 4/13 | 1 | NM_016219.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000128 AC: 32AN: 250338Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135570
GnomAD4 exome AF: 0.000109 AC: 160AN: 1461540Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79AN XY: 727032
GnomAD4 genome AF: 0.000112 AC: 17AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74484
ClinVar
Submissions by phenotype
Rafiq syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Apr 13, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 196 of the MAN1B1 protein (p.Arg196Cys). This variant is present in population databases (rs373430024, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MAN1B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 129572). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2023 | The c.586C>T (p.R196C) alteration is located in exon 4 (coding exon 4) of the MAN1B1 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the arginine (R) at amino acid position 196 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at