chr19-651615-C-T

Variant names:

• chr19-651615-C-T
• rs2030291406
• NM_194460.3:c.439G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_194460.3(RNF126):​c.439G>A​(p.Glu147Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. E147Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF126 NM_194460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

Genes affected

RNF126 (HGNC:21151): (ring finger protein 126) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF126	NM_194460.3	c.439G>A	p.Glu147Lys	missense_variant	Exon 4 of 9	ENST00000292363.10	NP_919442.1
RNF126	XM_047439069.1	c.439G>A	p.Glu147Lys	missense_variant	Exon 4 of 8		XP_047295025.1
RNF126	NM_001366018.1	c.362+77G>A		intron_variant	Intron 4 of 8		NP_001352947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF126	ENST00000292363.10	c.439G>A	p.Glu147Lys	missense_variant	Exon 4 of 9	1	NM_194460.3	ENSP00000292363.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1282230 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 626464

African (AFR) AF: 0.00 AC: 0 AN: 25668

American (AMR) AF: 0.00 AC: 0 AN: 19446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18006

East Asian (EAS) AF: 0.00 AC: 0 AN: 32372

South Asian (SAS) AF: 0.00 AC: 0 AN: 62964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3876

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029968

Other (OTH) AF: 0.00 AC: 0 AN: 52082

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Vest4		0.87
MutPred		0.51		Gain of methylation at E147 (P = 0.0043);
MVP		0.31
MPC		0.47
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.84
Mutation Taster		=52/48	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: rs2030291406; hg19: chr19-651615;