rs998599

chr9-17700368-G-Achr9-17700368-G-T

Variant summary

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

The NM_003026.5(SH3GL2):c.46-46698G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,890 control chromosomes in the GnomAD database, including 22,575 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 0.53 (22575 hom., cov: 32)
• Consequence: SH3GL2 NM_003026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL2	NM_003026.5	c.46-46698G>A		intron_variant		ENST00000380607.5
SH3GL2	XM_011518005.4	c.148-46698G>A		intron_variant
SH3GL2	XM_047423730.1	c.-60-46698G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL2	ENST00000380607.5	c.46-46698G>A		intron_variant		1	NM_003026.5	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81126 AN: 151772 Hom.: 22545 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.535 AC: 81216 AN: 151890 Hom.: 22575 Cov.: 32 AF XY: 0.539 AC XY: 40013 AN XY: 74228

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.512

Alfa AF: 0.457 Hom.: 27329

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.063
Dann	Benign	0.47

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: rs998599; hg19: chr9-17700366;