1-32937014-C-T

Variant summary

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

The NM_001300826.2(RNF19B):​c.1988G>A​(p.Arg663His) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RNF19B
NM_001300826.2 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77
Variant links:
Genes affected
RNF19B (HGNC:26886): (ring finger protein 19B) This gene encodes a multi-pass membrane protein containing two RING-type and one IBR-type zinc finger motifs. The encoded protin is an E3 ubiquitin-protein ligase that plays a role in the cytotoxic effects of natural killer (NK) cells. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes X and Y in a possible pseudoautosomal region. [provided by RefSeq, Jul 2014]

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 rank MANE Protein UniProt
RNF19BNM_001300826.2 linkc.1988G>A p.Arg663His missense_variant Exon 9 of 9 ENST00000235150.5 NP_001287755.1 Q6ZMZ0-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF19BENST00000235150.5 linkc.1988G>A p.Arg663His missense_variant Exon 9 of 9 1 NM_001300826.2 ENSP00000235150.4 Q6ZMZ0-4
RNF19BENST00000373456.11 linkc.1991G>A p.Arg664His missense_variant Exon 9 of 9 1 ENSP00000362555.7 Q6ZMZ0-1
RNF19BENST00000356990 linkc.*274G>A 3_prime_UTR_variant Exon 9 of 9 1 ENSP00000349482.5 Q6ZMZ0-2
ENSG00000287691ENST00000661031.1 linkn.363+2660C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152126
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251472
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461890
Hom.:
0
Cov.:
33
AF XY:
0.0000179
AC XY:
13
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.0000187
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1991G>A (p.R664H) alteration is located in exon 9 (coding exon 9) of the RNF19B gene. This alteration results from a G to A substitution at nucleotide position 1991, causing the arginine (R) at amino acid position 664 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
Benign
0.27
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.64
N;N
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.11
T;T
Polyphen
1.0
D;.
Vest4
0.72
MVP
0.12
MPC
1.4
ClinPred
0.78
D
GERP RS
5.0
Varity_R
0.53
gMVP
0.35

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: rs373889408; hg19: chr1-33402615; API