rs75442795
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_016219.5(MAN1B1):c.403G>A(p.Val135Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,613,966 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★★).
Frequency
Consequence
NM_016219.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAN1B1 | NM_016219.5 | c.403G>A | p.Val135Ile | missense_variant | 3/13 | ENST00000371589.9 | |
MAN1B1 | XM_006716945.5 | c.403G>A | p.Val135Ile | missense_variant | 3/12 | ||
MAN1B1 | NR_045720.2 | n.418G>A | non_coding_transcript_exon_variant | 3/13 | |||
MAN1B1 | NR_045721.2 | n.549G>A | non_coding_transcript_exon_variant | 4/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAN1B1 | ENST00000371589.9 | c.403G>A | p.Val135Ile | missense_variant | 3/13 | 1 | NM_016219.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00162 AC: 247AN: 152184Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000466 AC: 117AN: 251326Hom.: 0 AF XY: 0.000368 AC XY: 50AN XY: 135888
GnomAD4 exome AF: 0.000319 AC: 467AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.000290 AC XY: 211AN XY: 727110
GnomAD4 genome ? AF: 0.00164 AC: 250AN: 152302Hom.: 1 Cov.: 33 AF XY: 0.00172 AC XY: 128AN XY: 74472
ClinVar
Submissions by phenotype
Rafiq syndrome Pathogenic:1Benign:2
Likely pathogenic, flagged submission | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 03, 2019 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2016 | This alteration is classified as 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. - |
MAN1B1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 21, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at