10-97246304-G-A

Position:

chr10-97246304-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032900.6(ARHGAP19):c.961C>T(p.His321Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,613,792 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 19 hom. )

Consequence

ARHGAP19
NM_032900.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

ARHGAP19 (HGNC:23724): (Rho GTPase activating protein 19) Members of the ARHGAP family, such as ARHGAP19, encode negative regulators of Rho GTPases (see RHOA; MIM 165390), which are involved in cell migration, proliferation, and differentiation, actin remodeling, and G1 cell cycle progression (Lv et al., 2007 [PubMed 17454002]).[supplied by OMIM, Mar 2008]

ARHGAP19 links:

ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ARHGAP19-SLIT1 links:

ARHGAP19 (HGNC:):

ARHGAP19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053498745).

BP6

Variant 10-97246304-G-A is Benign according to our data. Variant chr10-97246304-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640736.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP19	NM_032900.6 linkuse as main transcript	c.961C>T	p.His321Tyr	missense_variant	7/12	ENST00000358531.9	NP_116289.4	Q14CB8-1
ARHGAP19	NM_001256423.2 linkuse as main transcript	c.934C>T	p.His312Tyr	missense_variant	7/12		NP_001243352.1	Q14CB8-3
ARHGAP19	NM_001204300.2 linkuse as main transcript	c.874C>T	p.His292Tyr	missense_variant	6/11		NP_001191229.1	Q14CB8-6
ARHGAP19-SLIT1	NR_037909.1 linkuse as main transcript	n.1007C>T		non_coding_transcript_exon_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP19	ENST00000358531.9 linkuse as main transcript	c.961C>T	p.His321Tyr	missense_variant	7/12	1	NM_032900.6	ENSP00000351333.4		Q14CB8-1
ARHGAP19-SLIT1	ENST00000479633.2 linkuse as main transcript	n.961C>T		non_coding_transcript_exon_variant	7/15	2		ENSP00000473567.1

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00347

AC:

871

AN:

251082

Hom.:

AF XY:

0.00340

AC XY:

461

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.00402

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00356

AC:

5208

AN:

1461572

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

2508

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000881

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.00340

AC:

518

AN:

152220

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00339

Hom.:

Bravo

AF:

0.00243

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00325

AC:

394

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ARHGAP19-SLIT1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.061

T;.;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.92

L;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

0.68

N;N;N

REVEL

Benign

0.075

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.19

MVP

0.15

MPC

0.25

ClinPred

0.0038

GERP RS

3.8

Varity_R

0.023

gMVP

0.40

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