Genetic Variant NM_144967.4:c.599C>A (chrX-131084258-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144967.4(ARHGAP36):c.599C>A(p.Ala200Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ARHGAP36
NM_144967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Publications

0 publications found

Variant links:

Genes affected

ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP36 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP36	NM_144967.4	MANE Select	c.599C>A	p.Ala200Asp	missense	Exon 5 of 12	NP_659404.2
ARHGAP36	NM_001282607.2		c.563C>A	p.Ala188Asp	missense	Exon 5 of 12	NP_001269536.1	Q6ZRI8-4
ARHGAP36	NM_001330651.1		c.191C>A	p.Ala64Asp	missense	Exon 4 of 11	NP_001317580.1	Q6ZRI8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP36	ENST00000276211.10	TSL:2 MANE Select	c.599C>A	p.Ala200Asp	missense	Exon 5 of 12	ENSP00000276211.5	Q6ZRI8-1
ARHGAP36	ENST00000370922.5	TSL:1	c.563C>A	p.Ala188Asp	missense	Exon 5 of 12	ENSP00000359960.1	Q6ZRI8-4
ARHGAP36	ENST00000412432.6	TSL:1	c.506C>A	p.Ala169Asp	missense	Exon 5 of 12	ENSP00000408515.2	Q6ZRI8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1096377

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361925

African (AFR)

AF:

0.00

AC:

AN:

26321

American (AMR)

AF:

0.00

AC:

AN:

34950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19270

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

53604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841421

Other (OTH)

AF:

0.00

AC:

AN:

46018

GnomAD4 genome

Cov.:

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

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.057

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.61

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.1

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Benign

0.093

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.17

MutPred

0.69

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.19

MPC

0.89

ClinPred

0.62

GERP RS

5.0

Varity_R

0.24

gMVP

0.97

Mutation Taster

=71/29

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over