Variant chr2-233182-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015677.4(SH3YL1):c.452C>T(p.Thr151Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000709 in 1,594,274 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 1 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.63

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]

SH3YL1 links:

Genome browser will be placed here

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=0.37930062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3YL1	NM_015677.4 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	6/10	ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10 linkuse as main transcript	c.452C>T	p.Thr151Met	missense_variant	6/10	1	NM_015677.4	ENSP00000348471	P1	Q96HL8-1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000620

AC:

AN:

241750

Hom.:

AF XY:

0.0000531

AC XY:

AN XY:

131800

show subpopulations

Gnomad AFR exome

AF:

0.000735

Gnomad AMR exome

AF:

0.0000629

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1442188

Hom.:

Cov.:

AF XY:

0.0000418

AC XY:

AN XY:

717614

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.0000473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

AF:

0.000270

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000894

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000173

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

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

Feb 03, 2022

The c.452C>T (p.T151M) alteration is located in exon 6 (coding exon 6) of the SH3YL1 gene. This alteration results from a C to T substitution at nucleotide position 452, causing the threonine (T) at amino acid position 151 to be replaced by a methionine (M). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;.;.;T;T;.;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;.;.;D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.38

T;T;T;T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.3

M;.;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.0

D;.;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

D;.;D;D;D;D;D

Sift4G

Uncertain

0.0030

.;D;D;.;.;D;D

Polyphen

1.0

D;D;D;D;D;D;.

Vest4

0.86

MVP

0.54

MPC

0.45

ClinPred

0.55

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over