rs3813455

Variant names:

• chrX-154675858-C-G
• rs3813455
• NM_001081573.3:c.*2320G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081573.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB3	NM_001081573.3	MANE Select	c.*2320G>C		3_prime_UTR	Exon 10 of 10	NP_001075042.1	Q8WWW8-2
	GAB3	NM_080612.4		c.*2320G>C		3_prime_UTR	Exon 10 of 10	NP_542179.1	Q8WWW8-1
	GAB3	NM_001282283.2		c.*2320G>C		3_prime_UTR	Exon 9 of 9	NP_001269212.1	Q8WWW8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB3	ENST00000424127.3	TSL:1 MANE Select	c.*2320G>C		3_prime_UTR	Exon 10 of 10	ENSP00000399588.2	Q8WWW8-2
	GAB3	ENST00000369575.7	TSL:1	c.*2320G>C		3_prime_UTR	Exon 10 of 10	ENSP00000358588.3	Q8WWW8-1
	GAB3	ENST00000496390.5	TSL:1	n.3631G>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 4548 AN: 111898 Hom.: 101 Cov.: 22

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00852 AC: 263 AN: 30873

American (AMR) AF: 0.0347 AC: 369 AN: 10634

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 72 AN: 2649

East Asian (EAS) AF: 0.0431 AC: 153 AN: 3552

South Asian (SAS) AF: 0.00187 AC: 5 AN: 2670

European-Finnish (FIN) AF: 0.0368 AC: 223 AN: 6063

Middle Eastern (MID) AF: 0.00926 AC: 2 AN: 216

European-Non Finnish (NFE) AF: 0.0636 AC: 3378 AN: 53081

Other (OTH) AF: 0.0307 AC: 47 AN: 1529

Alfa AF: 0.0499 Hom.: 264

Bravo AF: 0.0400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		0.43
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: rs3813455; hg19: chrX-153904135;