rs771734740

Variant names:

• chr1-32936951-C-A
• rs771734740
• NM_001300826.2:c.2051G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300826.2(RNF19B):​c.2051G>T​(p.Cys684Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF19B NM_001300826.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

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]

ENSG00000287691 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31483683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300826.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF19B	NM_001300826.2	MANE Select	c.2051G>T	p.Cys684Phe	missense	Exon 9 of 9	NP_001287755.1	Q6ZMZ0-4
	RNF19B	NM_153341.4		c.2054G>T	p.Cys685Phe	missense	Exon 9 of 9	NP_699172.2	Q6ZMZ0-1
	RNF19B	NM_001127361.3		c.*337G>T		3_prime_UTR	Exon 9 of 9	NP_001120833.1	Q6ZMZ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF19B	ENST00000235150.5	TSL:1 MANE Select	c.2051G>T	p.Cys684Phe	missense	Exon 9 of 9	ENSP00000235150.4	Q6ZMZ0-4
	RNF19B	ENST00000373456.11	TSL:1	c.2054G>T	p.Cys685Phe	missense	Exon 9 of 9	ENSP00000362555.7	Q6ZMZ0-1
	RNF19B	ENST00000356990.9	TSL:1	c.*337G>T		3_prime_UTR	Exon 9 of 9	ENSP00000349482.5	Q6ZMZ0-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152030 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251476 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461870 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152030 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74250

African (AFR) AF: 0.0000242 AC: 1 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.22
Sift	Uncertain	0.024	D
Sift4G	Benign	0.49	T
Polyphen		0.98	D
Vest4		0.61
MutPred		0.20		Loss of glycosylation at S690 (P = 0.1298)
MVP		0.17
MPC		0.95
ClinPred		0.54	D
GERP RS		5.1
Varity_R		0.52
gMVP		0.23
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs771734740; hg19: chr1-33402552;