Genetic Variant ARHGDIG:p.Pro82Leu (chr16-281917-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001176.4(ARHGDIG):c.245C>T(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,434,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ARHGDIG
NM_001176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

Publications

1 publications found

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:

ENSG00000286901 (HGNC:):

ENSG00000286901 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07102764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001176.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGDIG	NM_001176.4	MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 2 of 6	NP_001167.2	Q99819

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGDIG	ENST00000219409.8	TSL:1 MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 2 of 6	ENSP00000219409.3	Q99819
ARHGDIG	ENST00000414650.1	TSL:3	c.-80C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000410541.1	C9J3B5
ARHGDIG	ENST00000856700.1		c.287C>T	p.Pro96Leu	missense	Exon 2 of 6	ENSP00000526759.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

235634

AF XY:

0.0000307

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1434692

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

713252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32896

American (AMR)

AF:

0.00

AC:

AN:

44064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25394

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38474

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85944

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.0000100

AC:

AN:

1098968

Other (OTH)

AF:

0.00

AC:

AN:

59028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000168

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.25

M_CAP

Benign

0.049

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.80

PhyloP100

0.24

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.87

REVEL

Benign

0.0060

Sift

Benign

0.054

Sift4G

Benign

0.20

Polyphen

0.15

Vest4

0.21

MutPred

0.30

Loss of catalytic residue at P81 (P = 0.0151)

MVP

0.16

MPC

0.059

ClinPred

0.096

GERP RS

0.38

Varity_R

0.064

gMVP

0.13

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over