10-48450411-G-A

Variant names:

• chr10-48450411-G-A
• NM_021226.4:c.1718C>T

Variant summary

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

The NM_021226.4(ARHGAP22):​c.1718C>T​(p.Ala573Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ARHGAP22 NM_021226.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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]

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 (MetaRNN=0.036920846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4	c.1718C>T	p.Ala573Val	missense_variant	Exon 9 of 10	ENST00000249601.9	NP_067049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9	c.1718C>T	p.Ala573Val	missense_variant	Exon 9 of 10	1	NM_021226.4	ENSP00000249601.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418060 Hom.: 0 Cov.: 36 AF XY: 0.00000143 AC XY: 1 AN XY: 701552

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.61
DANN	Benign	0.46
DEOGEN2	Benign	0.022	T;T;T;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.64	T;T;T;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.037	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.42	N;N;N;N;N;N;N
REVEL	Benign	0.026
Sift	Benign	0.66	T;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T
Polyphen		0.0020	B;B;.;.;B;.;B
Vest4		0.027
MutPred		0.13		Loss of helix (P = 0.079);.;.;.;.;.;.;
MVP		0.16
MPC		0.17
ClinPred		0.035	T
GERP RS		-6.4
Varity_R		0.023
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-49658454;