Variant 2-233183-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015677.4(SH3YL1):c.451A>C(p.Thr151Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,436 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T151M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

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:

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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, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3YL1	NM_015677.4 linkuse as main transcript	c.451A>C	p.Thr151Pro	missense_variant	6/10	ENST00000356150.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3YL1	ENST00000356150.10 linkuse as main transcript	c.451A>C	p.Thr151Pro	missense_variant	6/10	1	NM_015677.4	P1	Q96HL8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.451A>C (p.T151P) alteration is located in exon 6 (coding exon 6) of the SH3YL1 gene. This alteration results from a A to C substitution at nucleotide position 451, causing the threonine (T) at amino acid position 151 to be replaced by a proline (P). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

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

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;.;.;D;D;T

M_CAP

Benign

0.069

MetaRNN

Pathogenic

0.91

D;D;D;D;D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.3

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

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.1

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

REVEL

Uncertain

0.45

Sift

Uncertain

0.0030

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

Sift4G

Uncertain

0.010

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

Polyphen

0.97

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

Vest4

0.78

MutPred

0.77

Loss of helix (P = 0.079);.;.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;.;

MVP

0.52

MPC

0.50

ClinPred

0.98

GERP RS

5.7

Varity_R

0.73

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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