1-161048370-T-A

Position:

• chr1-161048370-T-A

Variant summary

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

The NM_001025598.2(ARHGAP30):​c.2651A>T​(p.Glu884Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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=0.09159073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.2651A>T	p.Glu884Val	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.2651A>T	p.Glu884Val	missense_variant	12/12	2	NM_001025598.2	ENSP00000356992.3
ARHGAP30	ENST00000368015.1	c.2120A>T	p.Glu707Val	missense_variant	8/8	5		ENSP00000356994.1
ARHGAP30	ENST00000368016.7	c.2033-15A>T		intron_variant		5		ENSP00000356995.3
ARHGAP30	ENST00000461003.5	n.3433A>T		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 41 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Oct 24, 2024

The c.2651A>T (p.E884V) alteration is located in exon 12 (coding exon 12) of the ARHGAP30 gene. This alteration results from a A to T substitution at nucleotide position 2651, causing the glutamic acid (E) at amino acid position 884 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.068
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.74	P;.
Vest4		0.21
MutPred		0.083		Gain of helix (P = 0.0496);.;
MVP		0.23
MPC		0.11
ClinPred		0.56	D
GERP RS		3.6
La Branchor		0.28
BranchPoint Hunter		5.0
Varity_R		0.16
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs1022424712; hg19: chr1-161018160;