dbSNP rs1020292799: ARHGAP19:p.Gly406Arg (chr10-97235285-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032900.6(ARHGAP19):c.1216G>C(p.Gly406Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,568 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARHGAP19
NM_032900.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056190133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP19	NM_032900.6 link	c.1216G>C	p.Gly406Arg	missense_variant	Exon 9 of 12	ENST00000358531.9	NP_116289.4	Q14CB8-1
ARHGAP19	NM_001256423.2 link	c.1189G>C	p.Gly397Arg	missense_variant	Exon 9 of 12		NP_001243352.1	Q14CB8-3
ARHGAP19	NM_001204300.2 link	c.1129G>C	p.Gly377Arg	missense_variant	Exon 8 of 11		NP_001191229.1	Q14CB8-6
ARHGAP19-SLIT1	NR_037909.1 link	n.1262G>C		non_coding_transcript_exon_variant	Exon 9 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP19	ENST00000358531.9 link	c.1216G>C	p.Gly406Arg	missense_variant	Exon 9 of 12	1	NM_032900.6	ENSP00000351333.4		Q14CB8-1
ARHGAP19-SLIT1	ENST00000479633.2 link	n.1216G>C		non_coding_transcript_exon_variant	Exon 9 of 15	2		ENSP00000473567.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727042

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;.;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0080

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

0.54

N;N;N

REVEL

Benign

0.082

Sift

Benign

0.77

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.17

B;B;B

Vest4

0.29

MutPred

0.28

Gain of solvent accessibility (P = 0.0097);.;.;

MVP

0.23

MPC

0.26

ClinPred

0.24

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.047

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over