dbSNP rs770441770: RNF126:p.Val288Ala (chr19-648201-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194460.3(RNF126):c.863T>C(p.Val288Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. V288E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RNF126
NM_194460.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.03

Publications

0 publications found

Variant links:

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]

RNF126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1297192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF126	NM_194460.3 link	c.863T>C	p.Val288Ala	missense_variant	Exon 9 of 9	ENST00000292363.10	NP_919442.1	Q9BV68A0A024R206A8K0Q1
RNF126	NM_001366018.1 link	c.782T>C	p.Val261Ala	missense_variant	Exon 9 of 9		NP_001352947.1
RNF126	XM_047439069.1 link	c.*287T>C		downstream_gene_variant			XP_047295025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF126	ENST00000292363.10 link	c.863T>C	p.Val288Ala	missense_variant	Exon 9 of 9	1	NM_194460.3	ENSP00000292363.3		Q9BV68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000424

AC:

AN:

235976

AF XY:

0.00000781

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1453968

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33340

American (AMR)

AF:

0.00

AC:

AN:

43934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25956

East Asian (EAS)

AF:

0.00

AC:

AN:

39380

South Asian (SAS)

AF:

0.0000353

AC:

AN:

85044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108104

Other (OTH)

AF:

0.00

AC:

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0080

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.053

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

PhyloP100

9.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.63

N;.

REVEL

Benign

0.12

Sift

Benign

0.84

T;.

Sift4G

Benign

0.67

T;.

Vest4

0.14

MutPred

0.32

Loss of sheet (P = 0.0025);.;

MVP

0.082

MPC

0.32

ClinPred

0.22

GERP RS

3.8

Varity_R

0.088

Mutation Taster

=66/34

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over