rs1752656932

Variant names:

• chr4-151139813-C-T
• rs1752656932
• NM_001378122.1:c.2258G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378122.1(SH3D19):​c.2258G>A​(p.Gly753Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SH3D19 NM_001378122.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.289

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]

LOC107986196 (HGNC:):

ACMG classification

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=0.079477996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3D19	NM_001378122.1	c.2258G>A	p.Gly753Asp	missense_variant	Exon 13 of 20	ENST00000604030.7	NP_001365051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3D19	ENST00000604030.7	c.2258G>A	p.Gly753Asp	missense_variant	Exon 13 of 20	5	NM_001378122.1	ENSP00000488951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

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: 0.0000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1487G>A (p.G496D) alteration is located in exon 14 (coding exon 8) of the SH3D19 gene. This alteration results from a G to A substitution at nucleotide position 1487, causing the glycine (G) at amino acid position 496 to be replaced by an aspartic acid (D). 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	0.091
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.15
DEOGEN2	Benign	0.018	.;T;T;.;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.61	.;T;.;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.079	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;L;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.52	N;N;N;N;.;N
REVEL	Benign	0.034
Sift	Benign	0.091	T;T;T;T;.;T
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.0040	B;B;B;B;.;B
Vest4		0.23
MutPred		0.30		.;Loss of glycosylation at S495 (P = 0.0422);Loss of glycosylation at S495 (P = 0.0422);.;.;.;
MVP		0.31
MPC		0.15
ClinPred		0.039	T
GERP RS		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.28

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

Other links and lift over

dbSNP: rs1752656932; hg19: chr4-152060965;