chr2-218819-T-C

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015677.4(SH3YL1):​c.1021A>G​(p.Met341Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SH3YL1
NM_015677.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11458942).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3YL1NM_015677.4 linkuse as main transcriptc.1021A>G p.Met341Val missense_variant 10/10 ENST00000356150.10 NP_056492.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH3YL1ENST00000356150.10 linkuse as main transcriptc.1021A>G p.Met341Val missense_variant 10/101 NM_015677.4 ENSP00000348471 P1Q96HL8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJun 17, 2024The c.1021A>G (p.M341V) alteration is located in exon 10 (coding exon 10) of the SH3YL1 gene. This alteration results from a A to G substitution at nucleotide position 1021, causing the methionine (M) at amino acid position 341 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.079
.;.;.;T;T;.;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.70
T;T;.;.;T;T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.11
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.32
.;.;.;N;N;.;.
MutationTaster
Benign
0.92
N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.2
N;.;N;N;N;N;N
REVEL
Benign
0.097
Sift
Benign
0.16
T;.;T;T;T;T;T
Sift4G
Benign
0.21
.;T;T;.;.;T;T
Polyphen
0.0
B;B;B;B;B;B;.
Vest4
0.14
MutPred
0.50
.;.;.;Loss of disorder (P = 0.1382);Loss of disorder (P = 0.1382);.;.;
MVP
0.13
MPC
0.080
ClinPred
0.27
T
GERP RS
3.6
Varity_R
0.082
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1215099371; hg19: chr2-218819; API