Variant 11-46688206-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004308.5(ARHGAP1):c.284C>T(p.Pro95Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARHGAP1
NM_004308.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.35

Variant links:

Genes affected

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ARHGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARHGAP1	NM_004308.5 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/13	ENST00000311956.9	NP_004299.1
ARHGAP1	XM_047426933.1 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/13		XP_047282889.1
ARHGAP1	XM_024448520.2 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/12		XP_024304288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP1	ENST00000311956.9 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/13	1	NM_004308.5	ENSP00000310491	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727120

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 08, 2023

The c.284C>T (p.P95L) alteration is located in exon 4 (coding exon 3) of the ARHGAP1 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the proline (P) at amino acid position 95 to be replaced by a leucine (L). 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

Uncertain

0.56

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;.

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0080

D;.

Polyphen

0.99

D;.

Vest4

0.82

MutPred

0.42

Loss of catalytic residue at P94 (P = 0.0101);Loss of catalytic residue at P94 (P = 0.0101);

MVP

0.68

MPC

0.91

ClinPred

1.0

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.69

gMVP

0.52

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