2-143624237-A-T

Position:

• chr2-143624237-A-T

Variant summary

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

The NM_018460.4(ARHGAP15):​c.1108A>T​(p.Ser370Cys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP15 NM_018460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

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=0.15578678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP15	NM_018460.4	c.1108A>T	p.Ser370Cys	missense_variant	12/14	ENST00000295095.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP15	ENST00000295095.11	c.1108A>T	p.Ser370Cys	missense_variant	12/14	1	NM_018460.4	P1
ARHGAP15	ENST00000419455.1	n.315A>T		non_coding_transcript_exon_variant	3/3	5
ARHGAP15	ENST00000549436.5	n.270A>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Mar 30, 2024

The c.1108A>T (p.S370C) alteration is located in exon 12 (coding exon 11) of the ARHGAP15 gene. This alteration results from a A to T substitution at nucleotide position 1108, causing the serine (S) at amino acid position 370 to be replaced by a cysteine (C). 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	0.055
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.56		Gain of catalytic residue at S370 (P = 0.0332);
MVP		0.39
MPC		0.055
ClinPred		0.55	D
GERP RS		3.6
Varity_R		0.25
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-144381806;