chr2-234197-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015677.4(SH3YL1):c.367G>A(p.Gly123Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,108 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
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
SH3YL1
NM_015677.4 missense
NM_015677.4 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 7.47
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.897
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH3YL1 | NM_015677.4 | c.367G>A | p.Gly123Arg | missense_variant | 5/10 | ENST00000356150.10 | NP_056492.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH3YL1 | ENST00000356150.10 | c.367G>A | p.Gly123Arg | missense_variant | 5/10 | 1 | NM_015677.4 | ENSP00000348471 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000882 AC: 22AN: 249452Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135350
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GnomAD4 exome AF: 0.0000732 AC: 107AN: 1461812Hom.: 0 Cov.: 30 AF XY: 0.0000921 AC XY: 67AN XY: 727208
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74458
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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 | Dec 19, 2023 | The c.367G>A (p.G123R) alteration is located in exon 5 (coding exon 5) of the SH3YL1 gene. This alteration results from a G to A substitution at nucleotide position 367, causing the glycine (G) at amino acid position 123 to be replaced by an arginine (R). 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
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;.;.;D;D;.;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;.;.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;H;H;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D;D;D;D;D;D
Sift4G
Pathogenic
.;D;D;.;.;D;D;D;D
Polyphen
D;D;D;D;D;D;.;.;.
Vest4
MutPred
Loss of sheet (P = 0.0037);.;.;Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);.;.;.;.;
MVP
MPC
0.49
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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