11-100921525-A-T

Position:

• chr11-100921525-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152432.4(ARHGAP42):​c.518A>T​(p.Asn173Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: ARHGAP42 NM_152432.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98

Genes affected

ARHGAP42 (HGNC:26545): (Rho GTPase activating protein 42) This gene encodes a Rho GTPase-activating protein (RhoGAP), and member of the GRAF or BAR-PH family of proteins. Expression of this gene is enriched in vascular smooth muscle cells and the encoded protein inhibits RhoA activity to regulate vascular tone and control blood pressure. A mutation in the first intron of this gene modulates its expression and is associated with reduced blood pressure in human patients with borderline hypertension. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24221584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP42	NM_152432.4	c.518A>T	p.Asn173Ile	missense_variant	6/24	ENST00000298815.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP42	ENST00000298815.13	c.518A>T	p.Asn173Ile	missense_variant	6/24	5	NM_152432.4	P1
ARHGAP42	ENST00000524892.7	c.416A>T	p.Asn139Ile	missense_variant	5/23	5
ARHGAP42	ENST00000531183.1	c.86A>T	p.Asn29Ile	missense_variant	2/7	3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.518A>T (p.N173I) alteration is located in exon 6 (coding exon 6) of the ARHGAP42 gene. This alteration results from a A to T substitution at nucleotide position 518, causing the asparagine (N) at amino acid position 173 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.019	.;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0018
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.060	.;N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.16	.;B;.
Vest4		0.45
MutPred		0.44		.;Loss of disorder (P = 0.04);.;
MVP		0.20
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.40
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr11-100792256;