Genetic Variant ARHGDIA:c.*362G>T (chr17-81868514-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001301242.2(ARHGDIA):c.865G>T(p.Gly289Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,530,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

ARHGDIA
NM_001301242.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

ARHGDIA (HGNC:678): (Rho GDP dissociation inhibitor alpha) This gene encodes a protein that plays a key role in the regulation of signaling through Rho GTPases. The encoded protein inhibits the disassociation of Rho family members from GDP (guanine diphosphate), thereby maintaining these factors in an inactive state. Activity of this protein is important in a variety of cellular processes, and expression of this gene may be altered in tumors. Mutations in this gene have been found in individuals with nephrotic syndrome, type 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ARHGDIA links:

ENSG00000262413 (HGNC:):

ENSG00000262413 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-81868514-C-A is Benign according to our data. Variant chr17-81868514-C-A is described in ClinVar as [Benign]. Clinvar id is 3338251.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGDIA	NM_004309.6 link	c.*362G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000269321.12	NP_004300.1	P52565-1V9HWE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGDIA	ENST00000269321 link	c.*362G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004309.6	ENSP00000269321.7		P52565-1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000336

AC:

AN:

130958

Hom.:

AF XY:

0.000364

AC XY:

AN XY:

71412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000228

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000586

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000545

AC:

751

AN:

1378328

Hom.:

Cov.:

AF XY:

0.000527

AC XY:

358

AN XY:

679322

show subpopulations

Gnomad4 AFR exome

AF:

0.000159

Gnomad4 AMR exome

AF:

0.000368

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.000240

Gnomad4 NFE exome

AF:

0.000634

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000342

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000538

Hom.:

Bravo

AF:

0.000291

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 8

Benign:1

Jun 29, 2024

Dr.Nikuei Genetic Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.1

DANN

Benign

0.66

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