chr2-233229-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015677.4(SH3YL1):c.405G>T(p.Arg135Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,562,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015677.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3YL1 | NM_015677.4 | c.405G>T | p.Arg135Ser | missense_variant, splice_region_variant | 6/10 | ENST00000356150.10 | NP_056492.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH3YL1 | ENST00000356150.10 | c.405G>T | p.Arg135Ser | missense_variant, splice_region_variant | 6/10 | 1 | NM_015677.4 | ENSP00000348471 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000181 AC: 4AN: 220752Hom.: 0 AF XY: 0.0000248 AC XY: 3AN XY: 120818
GnomAD4 exome AF: 0.0000298 AC: 42AN: 1410788Hom.: 0 Cov.: 30 AF XY: 0.0000286 AC XY: 20AN XY: 700446
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.405G>T (p.R135S) alteration is located in exon 6 (coding exon 6) of the SH3YL1 gene. This alteration results from a G to T substitution at nucleotide position 405, causing the arginine (R) at amino acid position 135 to be replaced by a serine (S). 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