X-131081791-C-T

Variant names:

• chrX-131081791-C-T
• rs773226775
• NM_144967.4:c.126C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144967.4(ARHGAP36):​c.126C>T​(p.Asn42Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,098,241 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: ARHGAP36 NM_144967.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 0 publications found

Genes affected

ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.291 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144967.4. 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
	ARHGAP36	NM_144967.4	MANE Select	c.126C>T	p.Asn42Asn	synonymous	Exon 2 of 12	NP_659404.2
	ARHGAP36	NM_001282607.2		c.90C>T	p.Asn30Asn	synonymous	Exon 2 of 12	NP_001269536.1	Q6ZRI8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.126C>T	p.Asn42Asn	synonymous	Exon 2 of 12	ENSP00000276211.5	Q6ZRI8-1
	ARHGAP36	ENST00000370922.5	TSL:1	c.90C>T	p.Asn30Asn	synonymous	Exon 2 of 12	ENSP00000359960.1	Q6ZRI8-4
	ARHGAP36	ENST00000412432.6	TSL:1	c.33C>T	p.Asn11Asn	synonymous	Exon 2 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1098241 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 1 AN XY: 363595

African (AFR) AF: 0.0000379 AC: 1 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 842135

Other (OTH) AF: 0.0000217 AC: 1 AN: 46097

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs773226775; hg19: chrX-130215765;