rs10963243

Positions:

• chr9-17739136-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380607.5(SH3GL2):​c.46-7930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 152,174 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.058 (294 hom., cov: 32)
• Consequence: SH3GL2 ENST00000380607.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL2	NM_003026.5	c.46-7930A>G		intron_variant		ENST00000380607.5	NP_003017.1
SH3GL2	XM_011518005.4	c.148-7930A>G		intron_variant			XP_011516307.1
SH3GL2	XM_047423730.1	c.-60-7930A>G		intron_variant			XP_047279686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5	c.46-7930A>G		intron_variant		1	NM_003026.5	ENSP00000369981	P1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8775 AN: 152056 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.0512

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0576 AC: 8770 AN: 152174 Hom.: 294 Cov.: 32 AF XY: 0.0565 AC XY: 4204 AN XY: 74414

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0726 Hom.: 84

Bravo AF: 0.0531

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs10963243; hg19: chr9-17739134;