X-154717327-G-A

Position:

• chrX-154717327-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000424127.3(GAB3):​c.73-998C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.63 (15535 hom., 19795 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GAB3 ENST00000424127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

Genes affected

GAB3 (HGNC:17515): (GRB2 associated binding protein 3) This gene is a member of the GRB2-associated binding protein gene family. These proteins are scaffolding/docking proteins that are involved in several growth factor and cytokine signaling pathways, and they contain a pleckstrin homology domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. The protein encoded by this gene facilitates macrophage differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB3	NM_001081573.3	c.73-998C>T		intron_variant		ENST00000424127.3	NP_001075042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB3	ENST00000424127.3	c.73-998C>T		intron_variant		1	NM_001081573.3	ENSP00000399588	A2
GAB3	ENST00000369575.7	c.73-998C>T		intron_variant		1		ENSP00000358588	P4
GAB3	ENST00000496390.5	n.93-998C>T		intron_variant, non_coding_transcript_variant		1
GAB3	ENST00000369568.8	c.73-998C>T		intron_variant		2		ENSP00000358581	A2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 68448 AN: 109335 Hom.: 15534 Cov.: 22 AF XY: 0.625 AC XY: 19770 AN XY: 31631

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.650

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.626 AC: 68466 AN: 109386 Hom.: 15535 Cov.: 22 AF XY: 0.625 AC XY: 19795 AN XY: 31692

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.656

Alfa AF: 0.674 Hom.: 59659

Bravo AF: 0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.39

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: rs2664170; hg19: chrX-153945602;