chrX-63637846-C-CTGTG

Variant names:

• chrX-63637846-C-CTGTG
• rs10542660
• NM_001353921.2:c.*178_*181dupCACA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001353921.2(ARHGEF9):​c.*178_*181dupCACA variant causes a 3 prime UTR 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 0.0015 (2 hom., 19 hem., cov: 12)
  • Exomes 𝑓: 0.0011 (0 hom. 7 hem.)
• Consequence: ARHGEF9 NM_001353921.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

ARHGEF9 (HGNC:14561): (Cdc42 guanine nucleotide exchange factor 9) The protein encoded by this gene is a Rho-like GTPase that switches between the active (GTP-bound) state and inactive (GDP-bound) state to regulate CDC42 and other genes. This brain-specific protein also acts as an adaptor protein for the recruitment of gephyrin and together these proteins facilitate receceptor recruitement in GABAnergic and glycinergic synapses. Defects in this gene are the cause of startle disease with epilepsy (STHEE), also known as hyperekplexia with epilepsy, as well as several other types of cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF9	NM_001353921.2	c.*178_*181dupCACA		3_prime_UTR_variant	Exon 10 of 10	ENST00000671741.2	NP_001340850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF9	ENST00000671741	c.*178_*181dupCACA		3_prime_UTR_variant	Exon 10 of 10		NM_001353921.2	ENSP00000500715.1

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 142 AN: 97022 Hom.: 2 Cov.: 12 AF XY: 0.000800 AC XY: 19 AN XY: 23762

Gnomad AFR AF: 0.000466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00127

Gnomad SAS AF: 0.00142

Gnomad FIN AF: 0.000866

Gnomad MID AF: 0.00966

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00233

GnomAD4 exome AF: 0.00106 AC: 225 AN: 213192 Hom.: 0 Cov.: 0 AF XY: 0.000110 AC XY: 7 AN XY: 63440

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000440

Gnomad4 EAS exome AF: 0.000810

Gnomad4 SAS exome AF: 0.000264

Gnomad4 FIN exome AF: 0.000675

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00146 AC: 142 AN: 97036 Hom.: 2 Cov.: 12 AF XY: 0.000799 AC XY: 19 AN XY: 23786

Gnomad4 AFR AF: 0.000465

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00128

Gnomad4 SAS AF: 0.00144

Gnomad4 FIN AF: 0.000866

Gnomad4 NFE AF: 0.00181

Gnomad4 OTH AF: 0.00230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10542660; hg19: chrX-62857726;