3-15257029-C-T

Variant names:

• chr3-15257029-C-T
• NM_004844.5:c.974G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004844.5(SH3BP5):​c.974G>A​(p.Ser325Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3BP5 NM_004844.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69
• Publications: 0 publications found

Genes affected

SH3BP5 (HGNC:10827): (SH3 domain binding protein 5) Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

SH3BP5-AS1 (HGNC:44501): (SH3BP5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31291348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004844.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	NM_004844.5	MANE Select	c.974G>A	p.Ser325Asn	missense	Exon 8 of 9	NP_004835.2	O60239-1
	SH3BP5	NM_001018009.4		c.503G>A	p.Ser168Asn	missense	Exon 8 of 9	NP_001018009.2	O60239-2
	SH3BP5-AS1	NR_046084.1		n.2846C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	ENST00000383791.8	TSL:1 MANE Select	c.974G>A	p.Ser325Asn	missense	Exon 8 of 9	ENSP00000373301.3	O60239-1
	SH3BP5	ENST00000408919.7	TSL:1	c.503G>A	p.Ser168Asn	missense	Exon 8 of 9	ENSP00000386231.3	O60239-2
	SH3BP5-AS1	ENST00000420195.1	TSL:1	n.2846C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.11		Gain of glycosylation at S320 (P = 0.0138)
MVP		0.72
MPC		0.15
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.080
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr3-15298536;