10-48446152-A-T

Variant names:

• chr10-48446152-A-T
• rs1051509
• NM_021226.4:c.*239T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021226.4(ARHGAP22):​c.*239T>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGAP22 NM_021226.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 13 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	NM_021226.4	MANE Select	c.*239T>A		3_prime_UTR	Exon 10 of 10	NP_067049.2
	ARHGAP22	NR_045675.2		n.3170T>A		non_coding_transcript_exon	Exon 11 of 11
	ARHGAP22	NR_144642.2		n.3028T>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP22	ENST00000249601.9	TSL:1 MANE Select	c.*239T>A		3_prime_UTR	Exon 10 of 10	ENSP00000249601.4
	ARHGAP22	ENST00000477708.6	TSL:1	c.*239T>A		3_prime_UTR	Exon 2 of 2	ENSP00000422868.1
	ARHGAP22	ENST00000417247.6	TSL:2	c.*239T>A		3_prime_UTR	Exon 8 of 8	ENSP00000410054.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 405392 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 211628

African (AFR) AF: 0.00 AC: 0 AN: 11836

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12790

East Asian (EAS) AF: 0.00 AC: 0 AN: 28970

South Asian (SAS) AF: 0.00 AC: 0 AN: 35494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 248264

Other (OTH) AF: 0.00 AC: 0 AN: 23882

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 15113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.37

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: rs1051509; hg19: chr10-49654195;