1-32942286-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001300826.2(RNF19B):​c.1576G>A​(p.Gly526Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,612,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

RNF19B
NM_001300826.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11999062).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF19BNM_001300826.2 linkc.1576G>A p.Gly526Ser missense_variant Exon 7 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.1576G>A p.Gly526Ser missense_variant Exon 7 of 9 1 NM_001300826.2 ENSP00000235150.4 Q6ZMZ0-4
RNF19BENST00000373456.11 linkc.1579G>A p.Gly527Ser missense_variant Exon 7 of 9 1 ENSP00000362555.7 Q6ZMZ0-1
RNF19BENST00000356990.9 linkc.1576G>A p.Gly526Ser missense_variant Exon 7 of 9 1 ENSP00000349482.5 Q6ZMZ0-2
ENSG00000287691ENST00000661031.1 linkn.363+7932C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000995
AC:
25
AN:
251302
Hom.:
0
AF XY:
0.0000884
AC XY:
12
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000346
AC:
505
AN:
1460032
Hom.:
0
Cov.:
31
AF XY:
0.000322
AC XY:
234
AN XY:
725884
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000439
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152268
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000170
Hom.:
0
Bravo
AF:
0.0000907
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1579G>A (p.G527S) alteration is located in exon 7 (coding exon 7) of the RNF19B gene. This alteration results from a G to A substitution at nucleotide position 1579, causing the glycine (G) at amino acid position 527 to be replaced by a serine (S). 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
0.13
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.54
CADD
Pathogenic
26
DANN
Benign
0.58
DEOGEN2
Benign
0.056
T;.;.
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.90
N;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
0.26
N;N;N
REVEL
Benign
0.12
Sift
Benign
0.45
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.82
P;.;.
Vest4
0.61
MVP
0.10
MPC
0.98
ClinPred
0.077
T
GERP RS
4.2
Varity_R
0.14
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201645488; hg19: chr1-33407887; COSMIC: COSV52388390; API