Variant 6-127287680-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001242850.2(RNF146):c.1067T>G(p.Val356Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,560,242 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

RNF146
NM_001242850.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

Variant links:

Genes affected

RNF146 (HGNC:21336): (ring finger protein 146) Enables poly-ADP-D-ribose binding activity and ubiquitin-protein transferase activity. Involved in positive regulation of canonical Wnt signaling pathway; protein ubiquitination; and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF146 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28588867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF146	NM_001242850.2 linkuse as main transcript	c.1067T>G	p.Val356Gly	missense_variant	3/3	ENST00000368314.6	NP_001229779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF146	ENST00000368314.6 linkuse as main transcript	c.1067T>G	p.Val356Gly	missense_variant	3/3	2	NM_001242850.2	ENSP00000357297	A1	Q9NTX7-1
RNF146	ENST00000610153.1 linkuse as main transcript	c.1067T>G	p.Val356Gly	missense_variant	3/3	2		ENSP00000476814	A1	Q9NTX7-1
RNF146	ENST00000608991.5 linkuse as main transcript	c.1064T>G	p.Val355Gly	missense_variant	5/5	4		ENSP00000477168	P4	Q9NTX7-2
RNF146	ENST00000356799.6 linkuse as main transcript	c.*1072T>G		3_prime_UTR_variant	4/4	2		ENSP00000349253

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000852

AC:

AN:

1408276

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

696748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000625

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000461

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.1067T>G (p.V356G) alteration is located in exon 3 (coding exon 2) of the RNF146 gene. This alteration results from a T to G substitution at nucleotide position 1067, causing the valine (V) at amino acid position 356 to be replaced by a glycine (G). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;T;.;T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

.;T;T;.;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

N;.;N;.;.

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Uncertain

0.0030

.;.;D;.;D

Polyphen

0.97

D;D;.;D;.

Vest4

0.58

MutPred

0.28

Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);.;Loss of sheet (P = 0.0025);.;

MVP

0.54

MPC

0.90

ClinPred

0.66

GERP RS

5.8

Varity_R

0.56

gMVP

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over