Genetic Variant RNF126:p.Val288Glu (chr19-648201-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_194460.3(RNF126):c.863T>A(p.Val288Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 1,453,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RNF126
NM_194460.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.120604336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF126	NM_194460.3 link	c.863T>A	p.Val288Glu	missense_variant	Exon 9 of 9	ENST00000292363.10	NP_919442.1	Q9BV68A0A024R206A8K0Q1
RNF126	NM_001366018.1 link	c.782T>A	p.Val261Glu	missense_variant	Exon 9 of 9		NP_001352947.1
RNF126	XM_047439069.1 link	c.*287T>A		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>A	p.Val288Glu	missense_variant	Exon 9 of 9	1	NM_194460.3	ENSP00000292363.3		Q9BV68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000466

AC:

AN:

235976

AF XY:

0.0000312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000329

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:

0.00000688

AC:

AN:

1453968

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33340

American (AMR)

AF:

0.000228

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:

0.00

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: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.863T>A (p.V288E) alteration is located in exon 9 (coding exon 9) of the RNF126 gene. This alteration results from a T to A substitution at nucleotide position 863, causing the valine (V) at amino acid position 288 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PhyloP100

9.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.69

N;.

REVEL

Benign

0.17

Sift

Benign

0.083

T;.

Sift4G

Benign

0.17

T;.

Vest4

0.26

MutPred

0.31

Loss of sheet (P = 0.0025);.;

MVP

0.068

MPC

0.65

ClinPred

0.25

GERP RS

3.8

Varity_R

0.25

Mutation Taster

=56/44

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.

chr19-648201-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over