7-99385772-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_005720.4(ARPC1B):c.58C>T(p.Arg20Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000497 in 1,609,408 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R20H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005720.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARPC1B | ENST00000646101.2 | c.58C>T | p.Arg20Cys | missense_variant | Exon 2 of 10 | NM_005720.4 | ENSP00000496599.1 | |||
ENSG00000284292 | ENST00000638617.1 | c.1054C>T | p.Arg352Cys | missense_variant | Exon 9 of 17 | 5 | ENSP00000491073.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000108 AC: 26AN: 240064Hom.: 1 AF XY: 0.000123 AC XY: 16AN XY: 130004
GnomAD4 exome AF: 0.0000494 AC: 72AN: 1457210Hom.: 1 Cov.: 31 AF XY: 0.0000566 AC XY: 41AN XY: 724502
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 20 of the ARPC1B protein (p.Arg20Cys). This variant is present in population databases (rs750614736, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ARPC1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1497895). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ARPC1B protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at