Genetic Variant ARHGDIG:p.Pro82Arg (chr16-281917-C-G) – 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>G(p.Pro82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P82L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARHGDIG
NM_001176.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.113939434).

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>G	p.Pro82Arg	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>G	p.Pro82Arg	missense	Exon 2 of 6	ENSP00000219409.3	Q99819
ARHGDIG	ENST00000856700.1		c.287C>G	p.Pro96Arg	missense	Exon 2 of 6	ENSP00000526759.1
ARHGDIG	ENST00000447871.5	TSL:5	c.245C>G	p.Pro82Arg	missense	Exon 2 of 6	ENSP00000404435.1	A2ID99

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1434692

Hom.:

Cov.:

AF XY:

0.00000421

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:

0.00

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:

0.00

AC:

AN:

1098968

Other (OTH)

AF:

0.00

AC:

AN:

59028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.53

M_CAP

Benign

0.074

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

PhyloP100

0.24

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.080

Sift

Benign

0.051

Sift4G

Uncertain

0.038

Polyphen

0.45

Vest4

0.27

MutPred

0.33

Loss of catalytic residue at P81 (P = 0.0116)

MVP

0.25

MPC

0.16

ClinPred

0.18

GERP RS

0.38

Varity_R

0.10

gMVP

0.12

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

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

Publications

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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