8-144098981-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_030974.4(SHARPIN):c.1061G>A(p.Cys354Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000649 in 1,603,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_030974.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SHARPIN | ENST00000398712.7 | c.1061G>A | p.Cys354Tyr | missense_variant | Exon 8 of 9 | 1 | NM_030974.4 | ENSP00000381698.2 | ||
SHARPIN | ENST00000359551.6 | n.936G>A | non_coding_transcript_exon_variant | Exon 7 of 8 | 1 | ENSP00000352551.6 | ||||
SHARPIN | ENST00000532536.5 | c.185G>A | p.Cys62Tyr | missense_variant | Exon 3 of 3 | 3 | ENSP00000432355.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000293 AC: 7AN: 238714Hom.: 0 AF XY: 0.0000230 AC XY: 3AN XY: 130184
GnomAD4 exome AF: 0.0000710 AC: 103AN: 1451276Hom.: 0 Cov.: 31 AF XY: 0.0000581 AC XY: 42AN XY: 722342
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1061G>A (p.C354Y) alteration is located in exon 8 (coding exon 8) of the SHARPIN gene. This alteration results from a G to A substitution at nucleotide position 1061, causing the cysteine (C) at amino acid position 354 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at