1-161048247-G-T

Position:

• chr1-161048247-G-T

Variant summary

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

The NM_001025598.2(ARHGAP30):​c.2774C>A​(p.Ala925Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50

Genes affected

ARHGAP30 (HGNC:27414): (Rho GTPase activating protein 30) Predicted to enable GTPase activator activity. Predicted to be involved in small GTPase mediated signal transduction. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP30 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.2774C>A	p.Ala925Asp	missense_variant	12/12	ENST00000368013.8	NP_001020769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP30	ENST00000368013.8	c.2774C>A	p.Ala925Asp	missense_variant	12/12	2	NM_001025598.2	ENSP00000356992.3
ARHGAP30	ENST00000368015.1	c.2243C>A	p.Ala748Asp	missense_variant	8/8	5		ENSP00000356994.1
ARHGAP30	ENST00000368016.7	c.2141C>A	p.Ala714Asp	missense_variant	13/13	5		ENSP00000356995.3
ARHGAP30	ENST00000461003.5	n.3556C>A		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

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

Apr 16, 2024

The c.2774C>A (p.A925D) alteration is located in exon 12 (coding exon 12) of the ARHGAP30 gene. This alteration results from a C to A substitution at nucleotide position 2774, causing the alanine (A) at amino acid position 925 to be replaced by an aspartic acid (D). 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	.;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.040	D;T;D
Polyphen		0.97	.;D;.
Vest4		0.64
MutPred		0.31		.;Gain of sheet (P = 0.0149);.;
MVP		0.28
MPC		0.23
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.36

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: chr1-161018037;