chr12-98735616-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The ENST00000547776.6(ANKS1B):c.3691C>T(p.His1231Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 620,104 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Consequence
ENST00000547776.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKS1B | NM_152788.4 | c.3691C>T | p.His1231Tyr | missense_variant | 26/26 | ||
ANKS1B | NM_001352196.2 | c.1441C>T | p.His481Tyr | missense_variant | 13/13 | ||
ANKS1B | NM_001352197.2 | c.1369C>T | p.His457Tyr | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKS1B | ENST00000547776.6 | c.3691C>T | p.His1231Tyr | missense_variant | 26/26 | 1 | |||
ANKS1B | ENST00000547010.5 | c.2239C>T | p.His747Tyr | missense_variant | 18/18 | 1 | |||
ANKS1B | ENST00000549558.6 | c.1189C>T | p.His397Tyr | missense_variant | 11/11 | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248006Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134520
GnomAD4 exome AF: 0.00000161 AC: 1AN: 620104Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 338084
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 06, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ANKS1B-related conditions. This variant is present in population databases (rs758073552, ExAC 0.002%). This sequence change replaces histidine with tyrosine at codon 1231 of the ANKS1B protein (p.His1231Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at