rs3813455

Positions:

• chrX-154675858-C-G
• chrX-154675858-C-T

Variant summary

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

The NM_001081573.3(GAB3):​c.*2320G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 111,952 control chromosomes in the GnomAD database, including 101 homozygotes. There are 1,224 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 0.041 (101 hom., 1224 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GAB3 NM_001081573.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAB3	NM_001081573.3	c.*2320G>C		3_prime_UTR_variant	10/10	ENST00000424127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAB3	ENST00000424127.3	c.*2320G>C		3_prime_UTR_variant	10/10	1	NM_001081573.3	A2
GAB3	ENST00000369575.7	c.*2320G>C		3_prime_UTR_variant	10/10	1		P4
GAB3	ENST00000496390.5	n.3631G>C		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 4548 AN: 111898 Hom.: 101 Cov.: 22 AF XY: 0.0359 AC XY: 1223 AN XY: 34076

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0311

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0406 AC: 4546 AN: 111952 Hom.: 101 Cov.: 22 AF XY: 0.0359 AC XY: 1224 AN XY: 34140

Gnomad4 AFR AF: 0.00852

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0499 Hom.: 264

Bravo AF: 0.0400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.65

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: rs3813455; hg19: chrX-153904135;