chr2-231115-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_015677.4(SH3YL1):āc.610T>Cā(p.Tyr204His) variant causes a missense change. The variant allele was found at a frequency of 0.000192 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.00020 ( 0 hom. )
Consequence
SH3YL1
NM_015677.4 missense
NM_015677.4 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.62
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40061826).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3YL1 | NM_015677.4 | c.610T>C | p.Tyr204His | missense_variant | 7/10 | ENST00000356150.10 | NP_056492.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH3YL1 | ENST00000356150.10 | c.610T>C | p.Tyr204His | missense_variant | 7/10 | 1 | NM_015677.4 | ENSP00000348471 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249490Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135388
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GnomAD4 exome AF: 0.000203 AC: 297AN: 1461804Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 148AN XY: 727202
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74366
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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 18, 2021 | The c.610T>C (p.Y204H) alteration is located in exon 7 (coding exon 7) of the SH3YL1 gene. This alteration results from a T to C substitution at nucleotide position 610, causing the tyrosine (Y) at amino acid position 204 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D;D;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;M;M;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;D;D;N;N
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D;D;D
Sift4G
Uncertain
.;D;T;.;.;T;D;D
Polyphen
P;D;D;D;D;D;.;.
Vest4
MVP
MPC
0.29
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