chr1-16205633-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153213.5(ARHGEF19):​c.1486C>T​(p.Arg496Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,612,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ARHGEF19
NM_153213.5 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
Variant links:
Genes affected
ARHGEF19 (HGNC:26604): (Rho guanine nucleotide exchange factor 19) Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390).[supplied by OMIM, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGEF19NM_153213.5 linkc.1486C>T p.Arg496Cys missense_variant 9/16 ENST00000270747.8 NP_694945.2 Q8IW93-1B4DN02
ARHGEF19XM_011540706.4 linkc.1486C>T p.Arg496Cys missense_variant 10/17 XP_011539008.1 Q8IW93-1
ARHGEF19XR_946544.2 linkn.1632-208C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGEF19ENST00000270747.8 linkc.1486C>T p.Arg496Cys missense_variant 9/161 NM_153213.5 ENSP00000270747.3 Q8IW93-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000507
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:
0.000478
GnomAD3 exomes
AF:
0.0000364
AC:
9
AN:
247060
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133900
show subpopulations
Gnomad AFR exome
AF:
0.000377
Gnomad AMR exome
AF:
0.0000298
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:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1460332
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
726532
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.0000226
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152312
Hom.:
0
Cov.:
33
AF XY:
0.000161
AC XY:
12
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000505
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:
0.000473
Alfa
AF:
0.0000999
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

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 GeneticsMar 14, 2023The c.1486C>T (p.R496C) alteration is located in exon 9 (coding exon 8) of the ARHGEF19 gene. This alteration results from a C to T substitution at nucleotide position 1486, causing the arginine (R) at amino acid position 496 to be replaced by a cysteine (C). 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
Benign
0.22
BayesDel_addAF
Benign
-0.098
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.051
T
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.53
D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.55
MVP
0.73
MPC
1.1
ClinPred
0.92
D
GERP RS
4.6
Varity_R
0.80
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs142369162; hg19: chr1-16532128; COSMIC: COSV54616167; COSMIC: COSV54616167; API