Variant 4-151122116-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001378122.1(SH3D19):c.3119A>G(p.Tyr1040Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,914 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SH3D19
NM_001378122.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

SH3D19 (HGNC:30418): (SH3 domain containing 19) This gene encodes a multiple SH3 domain-containing protein, which interacts with other proteins, such as EBP and members of ADAM family, via the SH3 domains. This protein may be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1 by EBP, and regulation of ADAM proteins in the signaling of EGFR-ligand shedding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SH3D19 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3D19	NM_001378122.1 link	c.3119A>G	p.Tyr1040Cys	missense_variant	Exon 20 of 20	ENST00000604030.7	NP_001365051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3D19	ENST00000604030.7 link	c.3119A>G	p.Tyr1040Cys	missense_variant	Exon 20 of 20	5	NM_001378122.1	ENSP00000488951.1		A0A0U1RQE4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721028

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:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2348A>G (p.Y783C) alteration is located in exon 21 (coding exon 15) of the SH3D19 gene. This alteration results from a A to G substitution at nucleotide position 2348, causing the tyrosine (Y) at amino acid position 783 to be replaced by a cysteine (C). 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

0.60

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.20

.;T;T;.;.;.

Eigen

Benign

0.091

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

0.98

.;D;.;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.96

D;D;D;D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.8

.;M;M;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.5

D;D;D;D;.;D

REVEL

Uncertain

0.44

Sift

Pathogenic

0.0

D;D;D;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

0.86

P;D;D;P;.;P

Vest4

0.64

MutPred

0.88

.;Loss of disorder (P = 0.0976);Loss of disorder (P = 0.0976);.;.;.;

MVP

0.86

MPC

0.55

ClinPred

0.99

GERP RS

4.2

Varity_R

0.58

gMVP

0.73

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over