X-136667904-GGAGA-GGA

Variant names:

• chrX-136667904-GGA-G
• rs1057515778
• NM_004840.3:c.*123_*124delTC

Variant summary

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

The NM_004840.3(ARHGEF6):​c.*123_*124delTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 799,056 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0043 (0 hom. 1 hem.)
• Consequence: ARHGEF6 NM_004840.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

ARHGEF6 (HGNC:685): (Rac/Cdc42 guanine nucleotide exchange factor 6) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It may form a complex with G proteins and stimulate Rho-dependent signals. This protein is activated by PI3-kinase. Mutations in this gene can cause X-chromosomal non-specific cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF6	NM_004840.3	c.*123_*124delTC		3_prime_UTR_variant	Exon 22 of 22	ENST00000250617.7	NP_004831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF6	ENST00000250617	c.*123_*124delTC		3_prime_UTR_variant	Exon 22 of 22	1	NM_004840.3	ENSP00000250617.6
ARHGEF6	ENST00000370622	c.*123_*124delTC		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000359656.1
ARHGEF6	ENST00000370620	c.*123_*124delTC		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000359654.1

Frequencies

GnomAD3 genomes AF: 0.0000551 AC: 6 AN: 108897 Hom.: 0 Cov.: 22 AF XY: 0.0000315 AC XY: 1 AN XY: 31793

Gnomad AFR AF: 0.000167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000974

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00431 AC: 2972 AN: 690123 Hom.: 0 AF XY: 0.00000541 AC XY: 1 AN XY: 184705

Gnomad4 AFR exome AF: 0.00438

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00309

Gnomad4 EAS exome AF: 0.00277

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.00340

Gnomad4 NFE exome AF: 0.00478

Gnomad4 OTH exome AF: 0.00393

GnomAD4 genome AF: 0.0000551 AC: 6 AN: 108933 Hom.: 0 Cov.: 22 AF XY: 0.0000314 AC XY: 1 AN XY: 31837

Gnomad4 AFR AF: 0.000167

Gnomad4 AMR AF: 0.0000973

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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: rs1057515778; hg19: chrX-135750063;