chr2-218888-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015677.4(SH3YL1):āc.952T>Cā(p.Ser318Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
SH3YL1
NM_015677.4 missense
NM_015677.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3YL1 | NM_015677.4 | c.952T>C | p.Ser318Pro | missense_variant | 10/10 | ENST00000356150.10 | NP_056492.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH3YL1 | ENST00000356150.10 | c.952T>C | p.Ser318Pro | missense_variant | 10/10 | 1 | NM_015677.4 | ENSP00000348471 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249124Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135274
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727196
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2023 | The c.952T>C (p.S318P) alteration is located in exon 10 (coding exon 10) of the SH3YL1 gene. This alteration results from a T to C substitution at nucleotide position 952, causing the serine (S) at amino acid position 318 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;L;L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D;D
Sift4G
Uncertain
.;D;D;.;.;D;D
Polyphen
D;D;D;D;D;D;.
Vest4
MutPred
0.46
.;.;.;Loss of ubiquitination at K315 (P = 0.0992);Loss of ubiquitination at K315 (P = 0.0992);.;.;
MVP
MPC
0.49
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at