10-97259523-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032900.6(ARHGAP19):​c.719G>A​(p.Arg240His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

ARHGAP19
NM_032900.6 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
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-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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37514183).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGAP19NM_032900.6 linkuse as main transcriptc.719G>A p.Arg240His missense_variant 5/12 ENST00000358531.9 NP_116289.4 Q14CB8-1
ARHGAP19NM_001256423.2 linkuse as main transcriptc.692G>A p.Arg231His missense_variant 5/12 NP_001243352.1 Q14CB8-3
ARHGAP19NM_001204300.2 linkuse as main transcriptc.719G>A p.Arg240His missense_variant 5/11 NP_001191229.1 Q14CB8-6
ARHGAP19-SLIT1NR_037909.1 linkuse as main transcriptn.765G>A non_coding_transcript_exon_variant 5/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGAP19ENST00000358531.9 linkuse as main transcriptc.719G>A p.Arg240His missense_variant 5/121 NM_032900.6 ENSP00000351333.4 Q14CB8-1
ARHGAP19-SLIT1ENST00000479633.2 linkuse as main transcriptn.719G>A non_coding_transcript_exon_variant 5/152 ENSP00000473567.1

Frequencies

GnomAD3 genomes
AF:
0.000250
AC:
38
AN:
152080
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
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:
0.000338
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000131
AC:
33
AN:
251474
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
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:
0.000237
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000212
AC:
310
AN:
1461866
Hom.:
0
Cov.:
34
AF XY:
0.000199
AC XY:
145
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000263
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000250
AC:
38
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000200
Hom.:
0
Bravo
AF:
0.000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsJul 14, 2021The c.719G>A (p.R240H) alteration is located in exon 5 (coding exon 5) of the ARHGAP19 gene. This alteration results from a G to A substitution at nucleotide position 719, causing the arginine (R) at amino acid position 240 to be replaced by a histidine (H). 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
0.43
BayesDel_addAF
Benign
-0.017
T
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T;.;.;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.1
M;M;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.9
D;D;D;.
REVEL
Uncertain
0.32
Sift
Benign
0.036
D;D;D;.
Sift4G
Benign
0.081
T;T;T;.
Polyphen
1.0
D;D;D;.
Vest4
0.76
MVP
0.63
MPC
0.92
ClinPred
0.41
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.61

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.

Other links and lift over

dbSNP: rs147811749; hg19: chr10-99019280; API