X-81250486-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003022.3(SH3BGRL):​c.46-26498G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
• Consequence: SH3BGRL NM_003022.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGRL	NM_003022.3	c.46-26498G>C		intron_variant	Intron 1 of 3	ENST00000373212.6	NP_003013.1
SH3BGRL	XM_011531013.1	c.231+13206G>C		intron_variant	Intron 2 of 4		XP_011529315.1
SH3BGRL	XM_011531014.2	c.156+13206G>C		intron_variant	Intron 3 of 5		XP_011529316.1
SH3BGRL	XM_047442354.1	c.156+13206G>C		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>C		intron_variant	Intron 1 of 3	1	NM_003022.3	ENSP00000362308.5
SH3BGRL	ENST00000481106.5	n.259-26498G>C		intron_variant	Intron 2 of 4	1
SH3BGRL	ENST00000463546.5	n.92-26498G>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.41

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: rs12389790; hg19: chrX-80505985;