NM_001300826.2:c.1201A>C

Variant names:

• chr1-32945574-T-G
• rs200028105
• NM_001300826.2:c.1201A>C

Variant summary

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

The NM_001300826.2(RNF19B):​c.1201A>C​(p.Ile401Leu) variant causes a missense change. 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. I401V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF19B NM_001300826.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.27
• 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.1201A>C	p.Ile401Leu	missense	Exon 5 of 9	NP_001287755.1	Q6ZMZ0-4
	RNF19B	NM_153341.4		c.1204A>C	p.Ile402Leu	missense	Exon 5 of 9	NP_699172.2	Q6ZMZ0-1
	RNF19B	NM_001127361.3		c.1201A>C	p.Ile401Leu	missense	Exon 5 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.1201A>C	p.Ile401Leu	missense	Exon 5 of 9	ENSP00000235150.4	Q6ZMZ0-4
	RNF19B	ENST00000373456.11	TSL:1	c.1204A>C	p.Ile402Leu	missense	Exon 5 of 9	ENSP00000362555.7	Q6ZMZ0-1
	RNF19B	ENST00000356990.9	TSL:1	c.1201A>C	p.Ile401Leu	missense	Exon 5 of 9	ENSP00000349482.5	Q6ZMZ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.049	D
Sift4G	Benign	0.071	T
Polyphen		0.51	P
Vest4		0.68
MutPred		0.39		Loss of solvent accessibility (P = 0.0329)
MVP		0.13
MPC		0.53
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.93
Mutation Taster		=75/25	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: rs200028105; hg19: chr1-33411175;