Variant 16-282663-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001176.4(ARHGDIG):c.527A>C(p.Glu176Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARHGDIG
NM_001176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Variant links:

Genes affected

ARHGDIG (HGNC:680): (Rho GDP dissociation inhibitor gamma) The GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activation of GTPases by inhibiting the exchange of GDP for GTP. See ARHGDIB (MIM 602843).[supplied by OMIM, Nov 2010]

ARHGDIG links:

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ACMG classification

Classification made for transcript

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	UniProt
ARHGDIG	NM_001176.4 linkuse as main transcript	c.527A>C	p.Glu176Ala	missense_variant	6/6	ENST00000219409.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGDIG	ENST00000219409.8 linkuse as main transcript	c.527A>C	p.Glu176Ala	missense_variant	6/6	1	NM_001176.4	P1
ARHGDIG	ENST00000447871.5 linkuse as main transcript	c.509A>C	p.Glu170Ala	missense_variant	6/6	5
ARHGDIG	ENST00000414650.1 linkuse as main transcript	c.203A>C	p.Glu68Ala	missense_variant	6/6	3
ARHGDIG	ENST00000477621.1 linkuse as main transcript	n.1095A>C		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000847

AC:

AN:

236238

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449282

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

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

Oct 26, 2021

The c.527A>C (p.E176A) alteration is located in exon 6 (coding exon 6) of the ARHGDIG gene. This alteration results from a A to C substitution at nucleotide position 527, causing the glutamic acid (E) at amino acid position 176 to be replaced by an alanine (A). 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

0.13

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.96

Eigen

Benign

0.053

Eigen_PC

Benign

0.078

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

0.94

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.61

.;P;.

Vest4

0.61

MutPred

0.67

.;Loss of disorder (P = 0.0502);.;

MVP

0.51

MPC

0.19

ClinPred

0.69

GERP RS

3.9

Varity_R

0.15

gMVP

0.40

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