NM_001353921.2:c.*174_*181delCACACACA

Variant names:

• chrX-63637846-CTGTGTGTG-C
• rs10542660
• NM_001353921.2:c.*174_*181delCACACACA

Variant summary

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

The NM_001353921.2(ARHGEF9):​c.*174_*181delCACACACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 310,361 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., 22 hem., cov: 12)
  • Exomes 𝑓: 0.00036 (0 hom. 9 hem.)
• Consequence: ARHGEF9 NM_001353921.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

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 Hemizygotes in GnomAd4 at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF9	NM_001353921.2	c.*174_*181delCACACACA		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.*174_*181delCACACACA		3_prime_UTR_variant	Exon 10 of 10		NM_001353921.2	ENSP00000500715.1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 140 AN: 97023 Hom.: 1 Cov.: 12 AF XY: 0.000884 AC XY: 21 AN XY: 23763

Gnomad AFR AF: 0.00443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00148

Gnomad ASJ AF: 0.00167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000948

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000831

Gnomad OTH AF: 0.00233

GnomAD4 exome AF: 0.000356 AC: 76 AN: 213324 Hom.: 0 AF XY: 0.000142 AC XY: 9 AN XY: 63546

Gnomad4 AFR exome AF: 0.00468

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.000173

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.000450

GnomAD4 genome AF: 0.00145 AC: 141 AN: 97037 Hom.: 1 Cov.: 12 AF XY: 0.000925 AC XY: 22 AN XY: 23787

Gnomad4 AFR AF: 0.00446

Gnomad4 AMR AF: 0.00148

Gnomad4 ASJ AF: 0.00167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000957

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000831

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;