Variant 1-161048178-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025598.2(ARHGAP30):c.2843A>G(p.Lys948Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARHGAP30
NM_001025598.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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 links:

ARHGAP30 (HGNC:):

ARHGAP30 links:

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ACMG classification

Classification made for transcript

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=0.1856418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2 linkuse as main transcript	c.2843A>G	p.Lys948Arg	missense_variant	12/12	ENST00000368013.8	NP_001020769.1	Q7Z6I6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGAP30	ENST00000368013.8 linkuse as main transcript	c.2843A>G	p.Lys948Arg	missense_variant	12/12	2	NM_001025598.2	ENSP00000356992.3	Q7Z6I6-1
ARHGAP30	ENST00000368015.1 linkuse as main transcript	c.2312A>G	p.Lys771Arg	missense_variant	8/8	5		ENSP00000356994.1	A0A0A0MRJ8
ARHGAP30	ENST00000368016.7 linkuse as main transcript	c.2210A>G	p.Lys737Arg	missense_variant	13/13	5		ENSP00000356995.3	A0A0A0MRJ9
ARHGAP30	ENST00000461003.5 linkuse as main transcript	n.3625A>G		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.2843A>G (p.K948R) alteration is located in exon 12 (coding exon 12) of the ARHGAP30 gene. This alteration results from a A to G substitution at nucleotide position 2843, causing the lysine (K) at amino acid position 948 to be replaced by an arginine (R). 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

0.077

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.058

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.13

.;B;.

Vest4

0.21

MutPred

0.11

.;Loss of methylation at K948 (P = 0.0756);.;

MVP

0.47

MPC

0.035

ClinPred

0.84

GERP RS

5.0

Varity_R

0.11

gMVP

0.087

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over