rs796052167

Variant names:

• chr10-48604783-T-G
• rs796052167
• NM_021226.4:c.14A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_021226.4(ARHGAP22):​c.14A>C​(p.Lys5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K5N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP22 NM_021226.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.33
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24146125).
• BP6: Variant 10-48604783-T-G is Benign according to our data. Variant chr10-48604783-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 207877.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021226.4. 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
	ARHGAP22	NM_021226.4	MANE Select	c.14A>C	p.Lys5Thr	missense	Exon 1 of 10	NP_067049.2
	ARHGAP22	NM_001256024.2		c.14A>C	p.Lys5Thr	missense	Exon 1 of 10	NP_001242953.1	Q7Z5H3-2
	ARHGAP22	NM_001347735.2		c.14A>C	p.Lys5Thr	missense	Exon 1 of 9	NP_001334664.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.14A>C	p.Lys5Thr	missense	Exon 1 of 10	ENSP00000249601.4	Q7Z5H3-1
	ARHGAP22	ENST00000417912.6	TSL:1	c.14A>C	p.Lys5Thr	missense	Exon 1 of 10	ENSP00000412461.2	Q7Z5H3-2
	ARHGAP22	ENST00000868871.1		c.14A>C	p.Lys5Thr	missense	Exon 1 of 9	ENSP00000538930.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.3
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.39
MutPred		0.18		Gain of phosphorylation at K5 (P = 0.0119)
MVP		0.18
MPC		0.65
ClinPred		0.95	D
GERP RS		3.5
PromoterAI		0.054	Neutral
Varity_R		0.20
gMVP		0.39
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs796052167; hg19: chr10-49812828;