chrX-81250486-G-A

Variant names:

• chrX-81250486-G-A
• rs12389790
• NM_003022.3:c.46-26498G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003022.3(SH3BGRL):​c.46-26498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 110,278 control chromosomes in the GnomAD database, including 2,195 homozygotes. There are 7,272 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 0.22 (2195 hom., 7272 hem., cov: 22)
• Consequence: SH3BGRL NM_003022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGRL	NM_003022.3	c.46-26498G>A		intron_variant	Intron 1 of 3	ENST00000373212.6	NP_003013.1
SH3BGRL	XM_011531013.1	c.231+13206G>A		intron_variant	Intron 2 of 4		XP_011529315.1
SH3BGRL	XM_011531014.2	c.156+13206G>A		intron_variant	Intron 3 of 5		XP_011529316.1
SH3BGRL	XM_047442354.1	c.156+13206G>A		intron_variant	Intron 2 of 4		XP_047298310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGRL	ENST00000373212.6	c.46-26498G>A		intron_variant	Intron 1 of 3	1	NM_003022.3	ENSP00000362308.5
SH3BGRL	ENST00000481106.5	n.259-26498G>A		intron_variant	Intron 2 of 4	1
SH3BGRL	ENST00000463546.5	n.92-26498G>A		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 24508 AN: 110249 Hom.: 2196 Cov.: 22

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.222 AC: 24524 AN: 110278 Hom.: 2195 Cov.: 22 AF XY: 0.223 AC XY: 7272 AN XY: 32638

African (AFR) AF: 0.215 AC: 6547 AN: 30427

American (AMR) AF: 0.190 AC: 1995 AN: 10500

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 479 AN: 2637

East Asian (EAS) AF: 0.695 AC: 2415 AN: 3477

South Asian (SAS) AF: 0.416 AC: 1075 AN: 2584

European-Finnish (FIN) AF: 0.218 AC: 1210 AN: 5563

Middle Eastern (MID) AF: 0.236 AC: 50 AN: 212

European-Non Finnish (NFE) AF: 0.197 AC: 10369 AN: 52702

Other (OTH) AF: 0.219 AC: 329 AN: 1501

Alfa AF: 0.218 Hom.: 4658

Bravo AF: 0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs12389790; hg19: chrX-80505985;