dbSNP rs201645488: RNF19B:p.Gly526Arg (chr1-32942286-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001300826.2(RNF19B):c.1576G>C(p.Gly526Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G526S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RNF19B
NM_001300826.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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]

RNF19B links:

ENSG00000287691 (HGNC:):

ENSG00000287691 links:

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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
RNF19B	NM_001300826.2 link	c.1576G>C	p.Gly526Arg	missense_variant	Exon 7 of 9	ENST00000235150.5	NP_001287755.1	Q6ZMZ0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF19B	ENST00000235150.5 link	c.1576G>C	p.Gly526Arg	missense_variant	Exon 7 of 9	1	NM_001300826.2	ENSP00000235150.4	Q6ZMZ0-4
RNF19B	ENST00000373456.11 link	c.1579G>C	p.Gly527Arg	missense_variant	Exon 7 of 9	1		ENSP00000362555.7	Q6ZMZ0-1
RNF19B	ENST00000356990.9 link	c.1576G>C	p.Gly526Arg	missense_variant	Exon 7 of 9	1		ENSP00000349482.5	Q6ZMZ0-2
ENSG00000287691	ENST00000661031.1 link	n.363+7932C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;.

Eigen

Benign

-0.035

Eigen_PC

Benign

-0.026

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.078

T;D;T

Polyphen

1.0

D;.;.

Vest4

0.81

MutPred

0.43

Gain of MoRF binding (P = 0.0038);.;.;

MVP

0.093

MPC

1.4

ClinPred

0.92

GERP RS

4.2

Varity_R

0.33

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over