4-151133172-C-G

Variant names:

• chr4-151133172-C-G
• rs372532779
• NM_001378122.1:c.2551G>C

Variant summary

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

The NM_001378122.1(SH3D19):​c.2551G>C​(p.Glu851Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3D19 NM_001378122.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3D19	NM_001378122.1	c.2551G>C	p.Glu851Gln	missense_variant	Exon 16 of 20	ENST00000604030.7	NP_001365051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3D19	ENST00000604030.7	c.2551G>C	p.Glu851Gln	missense_variant	Exon 16 of 20	5	NM_001378122.1	ENSP00000488951.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1780G>C (p.E594Q) alteration is located in exon 17 (coding exon 11) of the SH3D19 gene. This alteration results from a G to C substitution at nucleotide position 1780, causing the glutamic acid (E) at amino acid position 594 to be replaced by a glutamine (Q). 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	0.20
BayesDel_addAF	Benign	-0.0050	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	.;T;T;.;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;D;.;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.83	.;L;L;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N;N;N;N;.;N
REVEL	Benign	0.20
Sift	Benign	0.10	T;T;T;T;.;T
Sift4G	Uncertain	0.0080	D;D;D;D;T;D
Polyphen		0.69	P;P;P;P;.;P
Vest4		0.61
MutPred		0.64		.;Gain of glycosylation at S591 (P = 0.0227);Gain of glycosylation at S591 (P = 0.0227);.;.;.;
MVP		0.66
MPC		0.50
ClinPred		0.87	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs372532779; hg19: chr4-152054324;