1-32936872-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001300826.2(RNF19B):​c.2130G>A​(p.Met710Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RNF19B
NM_001300826.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.037912935).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF19BNM_001300826.2 linkc.2130G>A p.Met710Ile 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.2130G>A p.Met710Ile missense_variant Exon 9 of 9 1 NM_001300826.2 ENSP00000235150.4 Q6ZMZ0-4
RNF19BENST00000373456.11 linkc.2133G>A p.Met711Ile missense_variant Exon 9 of 9 1 ENSP00000362555.7 Q6ZMZ0-1
RNF19BENST00000356990 linkc.*416G>A 3_prime_UTR_variant Exon 9 of 9 1 ENSP00000349482.5 Q6ZMZ0-2
ENSG00000287691ENST00000661031.1 linkn.363+2518C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
249352
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134638
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460004
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
726080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2133G>A (p.M711I) 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 2133, causing the methionine (M) at amino acid position 711 to be replaced by an isoleucine (I). 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
0.14
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.090
T;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.15
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.025
Sift
Benign
0.57
T;T
Sift4G
Benign
0.51
T;T
Polyphen
0.0
B;.
Vest4
0.043
MutPred
0.25
Loss of catalytic residue at M711 (P = 0.0269);.;
MVP
0.11
MPC
0.48
ClinPred
0.048
T
GERP RS
3.9
Varity_R
0.10
gMVP
0.072

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: rs748338174; hg19: chr1-33402473; API