rs5959087

Positions:

• chrX-81235960-G-A
• chrX-81235960-G-C

Variant summary

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

The NM_003022.3(SH3BGRL):​c.45+33715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 110,880 control chromosomes in the GnomAD database, including 1,688 homozygotes. There are 6,300 hemizygotes in GnomAD. 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 0.19 (1688 hom., 6300 hem., cov: 22)
• Consequence: SH3BGRL NM_003022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

Genes affected

SH3BGRL (HGNC:10823): (SH3 domain binding glutamate rich protein like) Predicted to enable SH3 domain binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SH3BGRL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BGRL	NM_003022.3	c.45+33715G>A		intron_variant		ENST00000373212.6	NP_003013.1
SH3BGRL	XM_011531014.2	c.-7-1158G>A		intron_variant			XP_011529316.1
SH3BGRL	XM_047442354.1	c.-7-1158G>A		intron_variant			XP_047298310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BGRL	ENST00000373212.6	c.45+33715G>A		intron_variant		1	NM_003022.3	ENSP00000362308.5
SH3BGRL	ENST00000481106.5	n.258+33384G>A		intron_variant		1
SH3BGRL	ENST00000463546.5	n.91+33240G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 20573 AN: 110825 Hom.: 1690 Cov.: 22 AF XY: 0.190 AC XY: 6279 AN XY: 33057

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0850

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.214

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.186 AC: 20589 AN: 110880 Hom.: 1688 Cov.: 22 AF XY: 0.190 AC XY: 6300 AN XY: 33122

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.195

Alfa AF: 0.207 Hom.: 4842

Bravo AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.79

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: rs5959087; hg19: chrX-80491459;