X-154706415-CAAAA-CAA

Variant names:

• chrX-154706415-CAA-C
• rs35975601
• NM_001081573.3:c.1069+5812_1069+5813delTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001081573.3(GAB3):​c.1069+5812_1069+5813delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0013 (0 hom., 14 hem., cov: 0)
• Consequence: GAB3 NM_001081573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 14 gene

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.1069+5812_1069+5813delTT		intron	N/A	NP_001075042.1	Q8WWW8-2
	GAB3	NM_080612.4		c.1066+5812_1066+5813delTT		intron	N/A	NP_542179.1	Q8WWW8-1
	GAB3	NM_001282283.2		c.1069+5812_1069+5813delTT		intron	N/A	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.1069+5812_1069+5813delTT		intron	N/A	ENSP00000399588.2	Q8WWW8-2
	GAB3	ENST00000369575.7	TSL:1	c.1066+5812_1066+5813delTT		intron	N/A	ENSP00000358588.3	Q8WWW8-1
	GAB3	ENST00000496390.5	TSL:1	n.617-6358_617-6357delTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 117 AN: 93458 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000937

Gnomad ASJ AF: 0.00126

Gnomad EAS AF: 0.00131

Gnomad SAS AF: 0.000497

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.00488

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00125 AC: 117 AN: 93454 Hom.: 0 Cov.: 0 AF XY: 0.000681 AC XY: 14 AN XY: 20548

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000242 AC: 6 AN: 24760

American (AMR) AF: 0.000936 AC: 8 AN: 8544

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 3 AN: 2382

East Asian (EAS) AF: 0.00132 AC: 4 AN: 3028

South Asian (SAS) AF: 0.000500 AC: 1 AN: 2001

European-Finnish (FIN) AF: 0.00763 AC: 26 AN: 3407

Middle Eastern (MID) AF: 0.00538 AC: 1 AN: 186

European-Non Finnish (NFE) AF: 0.00144 AC: 68 AN: 47295

Other (OTH) AF: 0.00 AC: 0 AN: 1248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35975601; hg19: chrX-153934690;