chr8-144099820-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_030974.4(SHARPIN):c.542G>A(p.Arg181Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,562 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R181W) has been classified as Uncertain significance.
Frequency
Consequence
NM_030974.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHARPIN | NM_030974.4 | c.542G>A | p.Arg181Gln | missense_variant | 4/9 | ENST00000398712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHARPIN | ENST00000398712.7 | c.542G>A | p.Arg181Gln | missense_variant | 4/9 | 1 | NM_030974.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000323 AC: 8AN: 247454Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134734
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1460386Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 726568
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74336
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2023 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at