NM_001300826.2:c.2149G>T

Variant names:

• chr1-32936853-C-A
• rs371235809
• NM_001300826.2:c.2149G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001300826.2(RNF19B):​c.2149G>T​(p.Glu717*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,444,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: RNF19B NM_001300826.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• Publications: 4 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2149G>T	p.Glu717*	stop_gained	Exon 9 of 9	NP_001287755.1	Q6ZMZ0-4
	RNF19B	NM_153341.4		c.2152G>T	p.Glu718*	stop_gained	Exon 9 of 9	NP_699172.2	Q6ZMZ0-1
	RNF19B	NM_001127361.3		c.*435G>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.2149G>T	p.Glu717*	stop_gained	Exon 9 of 9	ENSP00000235150.4	Q6ZMZ0-4
	RNF19B	ENST00000373456.11	TSL:1	c.2152G>T	p.Glu718*	stop_gained	Exon 9 of 9	ENSP00000362555.7	Q6ZMZ0-1
	RNF19B	ENST00000356990.9	TSL:1	c.*435G>T		3_prime_UTR	Exon 9 of 9	ENSP00000349482.5	Q6ZMZ0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000826 AC: 2 AN: 242174 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000284 AC: 41 AN: 1444340 Hom.: 0 Cov.: 33 AF XY: 0.0000265 AC XY: 19 AN XY: 715680

African (AFR) AF: 0.00 AC: 0 AN: 33208

American (AMR) AF: 0.00 AC: 0 AN: 43712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.0000373 AC: 41 AN: 1100416

Other (OTH) AF: 0.00 AC: 0 AN: 59598

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		3.5
Vest4		0.21
GERP RS		5.3
Mutation Taster		=63/137	disease causing

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: rs371235809; hg19: chr1-33402454; COSMIC: COSV52390122;