9-129009146-T-C

Position:

• chr9-129009146-T-C

Variant summary

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

The NM_020145.4(SH3GLB2):​c.1040A>G​(p.Glu347Gly) 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: SH3GLB2 NM_020145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

Genes affected

SH3GLB2 (HGNC:10834): (SH3 domain containing GRB2 like, endophilin B2) Enables identical protein binding activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH3GLB2 (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/exons	MANE	Protein	UniProt
SH3GLB2	NM_020145.4	c.1040A>G	p.Glu347Gly	missense_variant	10/11	ENST00000372564.8	NP_064530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GLB2	ENST00000372564.8	c.1040A>G	p.Glu347Gly	missense_variant	10/11	1	NM_020145.4	ENSP00000361645.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.1040A>G (p.E347G) alteration is located in exon 10 (coding exon 10) of the SH3GLB2 gene. This alteration results from a A to G substitution at nucleotide position 1040, causing the glutamic acid (E) at amino acid position 347 to be replaced by a glycine (G). 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	Uncertain	0.38
BayesDel_addAF	Benign	0.0019	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;T;.;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.6	L;L;.;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		0.87	P;P;P;.;.
Vest4		0.41
MutPred		0.54		Loss of stability (P = 0.0884);Loss of stability (P = 0.0884);.;.;.;
MVP		0.78
MPC		0.76
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.36
gMVP		0.51

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.

Other links and lift over

hg19: chr9-131771425;