rs141833472
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2
The NM_006005.3(WFS1):āc.2563T>Cā(p.Ser855Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,613,052 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S855L) has been classified as Uncertain significance.
Frequency
Consequence
NM_006005.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WFS1 | NM_006005.3 | c.2563T>C | p.Ser855Pro | missense_variant | 8/8 | ENST00000226760.5 | |
WFS1 | NM_001145853.1 | c.2563T>C | p.Ser855Pro | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WFS1 | ENST00000226760.5 | c.2563T>C | p.Ser855Pro | missense_variant | 8/8 | 1 | NM_006005.3 | P2 | |
ENST00000661896.1 | n.1337+1557A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152262Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.000492 AC: 123AN: 250128Hom.: 1 AF XY: 0.000627 AC XY: 85AN XY: 135618
GnomAD4 exome AF: 0.000405 AC: 591AN: 1460672Hom.: 3 Cov.: 99 AF XY: 0.000489 AC XY: 355AN XY: 726686
GnomAD4 genome AF: 0.000269 AC: 41AN: 152380Hom.: 0 Cov.: 35 AF XY: 0.000215 AC XY: 16AN XY: 74528
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 30, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 05, 2020 | This variant is associated with the following publications: (PMID: 15605410, 12707373) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | WFS1: BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Monogenic diabetes Benign:1
Likely benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | May 22, 2017 | ACMG Criteria:BP4 (9 predictors), BS2 (4 cases and 14 controls in type2diabetesgenetics.org, and 1 South Asian homozygote in ExAC) - |
Wolfram syndrome 1 Benign:1
Benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. rs141833472 variant is also seen in patients with Diabetes Mellitus. However, the role of this particular variant is yet to be ascertained. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at