chr1-16205633-G-A
Position:
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
NM_153213.5 missense
Scores
4
11
4
Clinical Significance
Conservation
PhyloP100: 4.08
Genes affected
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 |
---|---|---|---|---|---|---|---|---|
ARHGEF19 | NM_153213.5 | c.1486C>T | p.Arg496Cys | missense_variant | 9/16 | ENST00000270747.8 | NP_694945.2 | |
ARHGEF19 | XM_011540706.4 | c.1486C>T | p.Arg496Cys | missense_variant | 10/17 | XP_011539008.1 | ||
ARHGEF19 | XR_946544.2 | n.1632-208C>T | intron_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152194Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
23
AN:
152194
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247060Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133900
GnomAD3 exomes
AF:
AC:
9
AN:
247060
Hom.:
AF XY:
AC XY:
3
AN XY:
133900
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460332Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 726532
GnomAD4 exome
AF:
AC:
25
AN:
1460332
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
726532
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000151 AC: 23AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74482
GnomAD4 genome
AF:
AC:
23
AN:
152312
Hom.:
Cov.:
33
AF XY:
AC XY:
12
AN XY:
74482
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
3
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
4
EpiCase
AF:
EpiControl
AF:
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 submitter | clinical testing | Ambry Genetics | Mar 14, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at