chr10-48656239-C-G

Position:

• chr10-48656239-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001347738.2(ARHGAP22):​c.-326G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 142,960 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.0017 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP22 NM_001347738.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ARHGAP22 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP22	NM_001347738.2	c.-326G>C		5_prime_UTR_variant	1/11		NP_001334667.1
ARHGAP22	NM_001347736.2	c.-326G>C		5_prime_UTR_variant	1/4		NP_001334665.1
ARHGAP22	XM_011540002.3	c.-842G>C		5_prime_UTR_variant	1/11		XP_011538304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000460425.1	n.-842G>C		non_coding_transcript_exon_variant	1/11	2		ENSP00000422663.1
ARHGAP22	ENST00000460425.1	n.-842G>C		5_prime_UTR_variant	1/11	2		ENSP00000422663.1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 244 AN: 142886 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00933

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00153

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 116 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 100

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00171 AC: 244 AN: 142960 Hom.: 1 Cov.: 29 AF XY: 0.00175 AC XY: 122 AN XY: 69616

Gnomad4 AFR AF: 0.000196

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00933

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00111

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00268

Gnomad4 OTH AF: 0.00151

Alfa AF: 0.000241 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77568722; hg19: chr10-49864284;