chr1-161047951-C-T

Position:

• chr1-161047951-C-T

Variant summary

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

The NM_001025598.2(ARHGAP30):​c.3070G>A​(p.Gly1024Ser) 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. 14/21 in silico tools predict 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)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.556

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11676249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.3070G>A	p.Gly1024Ser	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.3070G>A	p.Gly1024Ser	missense_variant	12/12	2	NM_001025598.2	ENSP00000356992.3
ARHGAP30	ENST00000368015.1	c.2539G>A	p.Gly847Ser	missense_variant	8/8	5		ENSP00000356994.1
ARHGAP30	ENST00000368016.7	c.2437G>A	p.Gly813Ser	missense_variant	13/13	5		ENSP00000356995.3
ARHGAP30	ENST00000461003.5	n.3852G>A		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

Aug 27, 2024

The c.3070G>A (p.G1024S) alteration is located in exon 12 (coding exon 12) of the ARHGAP30 gene. This alteration results from a G to A substitution at nucleotide position 3070, causing the glycine (G) at amino acid position 1024 to be replaced by a serine (S). 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	0.081
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.55	T;T;D
Polyphen		0.11	.;B;.
Vest4		0.11
MutPred		0.26		.;Gain of glycosylation at G1024 (P = 0.018);.;
MVP		0.37
MPC		0.034
ClinPred		0.60	D
GERP RS		3.9
Varity_R		0.17
gMVP		0.13

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: chr1-161017741;