rs201744899

Variant names:

• chr19-650280-C-G
• rs201744899
• NM_194460.3:c.460G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-650280-C-G
• chr19-650280-C-T

Variant summary

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

The NM_194460.3(RNF126):​c.460G>C​(p.Val154Leu) 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. V154I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF126 NM_194460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF126	NM_194460.3	c.460G>C	p.Val154Leu	missense_variant	Exon 5 of 9	ENST00000292363.10	NP_919442.1
RNF126	NM_001366018.1	c.379G>C	p.Val127Leu	missense_variant	Exon 5 of 9		NP_001352947.1
RNF126	XM_047439069.1	c.460G>C	p.Val154Leu	missense_variant	Exon 5 of 8		XP_047295025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF126	ENST00000292363.10	c.460G>C	p.Val154Leu	missense_variant	Exon 5 of 9	1	NM_194460.3	ENSP00000292363.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.63
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PhyloP100		5.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N;.
REVEL	Benign	0.21
Sift	Benign	0.59	T;.
Sift4G	Benign	1.0	T;.
Vest4		0.72
MutPred		0.40		Gain of catalytic residue at V154 (P = 0.0107);.;
MVP		0.28
MPC		0.74
ClinPred		0.82	D
GERP RS		4.1
Varity_R		0.22
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201744899; hg19: chr19-650280;