1-32942386-C-A

Variant names:

• chr1-32942386-C-A
• rs1309593933
• NM_001300826.2:c.1476G>T

Variant summary

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

The NM_001300826.2(RNF19B):​c.1476G>T​(p.Leu492Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF19B NM_001300826.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• 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 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.1476G>T	p.Leu492Phe	missense	Exon 7 of 9	NP_001287755.1	Q6ZMZ0-4
	RNF19B	NM_153341.4		c.1479G>T	p.Leu493Phe	missense	Exon 7 of 9	NP_699172.2	Q6ZMZ0-1
	RNF19B	NM_001127361.3		c.1476G>T	p.Leu492Phe	missense	Exon 7 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.1476G>T	p.Leu492Phe	missense	Exon 7 of 9	ENSP00000235150.4	Q6ZMZ0-4
	RNF19B	ENST00000373456.11	TSL:1	c.1479G>T	p.Leu493Phe	missense	Exon 7 of 9	ENSP00000362555.7	Q6ZMZ0-1
	RNF19B	ENST00000356990.9	TSL:1	c.1476G>T	p.Leu492Phe	missense	Exon 7 of 9	ENSP00000349482.5	Q6ZMZ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461718 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.62
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.77
MutPred		0.27		Loss of loop (P = 0.0112)
MVP		0.14
MPC		1.3
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.37
gMVP		0.66
Mutation Taster		=71/29	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: rs1309593933; hg19: chr1-33407987;