rs35975601

chrX-154706415-CAAA-CchrX-154706415-CAAA-CAchrX-154706415-CAAA-CAAchrX-154706415-CAAA-CAAAAchrX-154706415-CAAA-CAAAAAchrX-154706415-CAAA-CAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001081573.3(GAB3):c.1069+5811_1069+5813del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 93,543 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000011 (0 hom., 0 hem., cov: 0)
• Consequence: GAB3 NM_001081573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB3	NM_001081573.3	c.1069+5811_1069+5813del		intron_variant		ENST00000424127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB3	ENST00000424127.3	c.1069+5811_1069+5813del		intron_variant		1	NM_001081573.3	A2
GAB3	ENST00000369575.7	c.1066+5811_1066+5813del		intron_variant		1		P4
GAB3	ENST00000496390.5	n.617-6359_617-6357del		intron_variant, non_coding_transcript_variant		1
GAB3	ENST00000369568.8	c.1069+5811_1069+5813del		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0000107 AC: 1 AN: 93543 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20595

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000211

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000107 AC: 1 AN: 93543 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20595

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000211

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35975601; hg19: chrX-153934690;