15-32629642-A-G

Position:

chr15-32629642-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014783.6(ARHGAP11A):c.985A>G(p.Thr329Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,562 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 11 hom., cov: 27)

Exomes 𝑓: 0.00062 ( 7 hom. )

Consequence

ARHGAP11A
NM_014783.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.42

Variant links:

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A links:

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 links:

ENSG00000285948 (HGNC:):

ENSG00000285948 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007574767).

BP6

Variant 15-32629642-A-G is Benign according to our data. Variant chr15-32629642-A-G is described in ClinVar as [Benign]. Clinvar id is 785480.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00603 (919/152336) while in subpopulation AFR AF= 0.021 (872/41578). AF 95% confidence interval is 0.0198. There are 11 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP11A	NM_014783.6 link	c.985A>G	p.Thr329Ala	missense_variant	8/12	ENST00000361627.8	NP_055598.1	Q6P4F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP11A	ENST00000361627.8 link	c.985A>G	p.Thr329Ala	missense_variant	8/12	1	NM_014783.6	ENSP00000355090.3		Q6P4F7-1
ARHGAP11A-SCG5	ENST00000692248.1 link	c.985A>G	p.Thr329Ala	missense_variant	8/14			ENSP00000510771.1		A0A8I5KWH8

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

919

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00168

AC:

420

AN:

250600

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.000877

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:

0.00000881

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000615

AC:

899

AN:

1461226

Hom.:

Cov.:

AF XY:

0.000542

AC XY:

394

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00603

AC:

919

AN:

152336

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00703

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00208

AC:

253

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

.;T;.;.;.

Eigen

Benign

-0.053

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.46

.;T;T;.;T

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.0

.;N;N;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.10

N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.0

.;B;.;.;.

Vest4

0.32

MVP

0.85

MPC

0.032

ClinPred

0.056

GERP RS

5.4

Varity_R

0.12

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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