Variant 6-127287583-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001242850.2(RNF146):c.970G>A(p.Asp324Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,612,548 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 4 hom. )

Consequence

RNF146
NM_001242850.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058784485).

BP6

Variant 6-127287583-G-A is Benign according to our data. Variant chr6-127287583-G-A is described in ClinVar as [Benign]. Clinvar id is 734128.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF146	NM_001242850.2 linkuse as main transcript	c.970G>A	p.Asp324Asn	missense_variant	3/3	ENST00000368314.6	NP_001229779.1	Q9NTX7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF146	ENST00000368314.6 linkuse as main transcript	c.970G>A	p.Asp324Asn	missense_variant	3/3	2	NM_001242850.2	ENSP00000357297.1	Q9NTX7-1
RNF146	ENST00000610153.1 linkuse as main transcript	c.970G>A	p.Asp324Asn	missense_variant	3/3	2		ENSP00000476814.1	Q9NTX7-1
RNF146	ENST00000608991.5 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	5/5	4		ENSP00000477168.1	Q9NTX7-2
RNF146	ENST00000356799.6 linkuse as main transcript	c.*975G>A		3_prime_UTR_variant	4/4	2		ENSP00000349253.3	V9GYY4

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

484

AN:

151690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000825

AC:

206

AN:

249746

Hom.:

AF XY:

0.000637

AC XY:

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.00969

Gnomad AMR exome

AF:

0.000668

Gnomad ASJ exome

AF:

0.000798

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000890

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.000413

AC:

604

AN:

1460742

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

262

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00319

AC:

484

AN:

151806

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

222

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0106

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000599

Hom.:

Bravo

AF:

0.00407

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000989

AC:

120

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0029

T;T;.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

.;T;T;.;.

MetaRNN

Benign

0.0059

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.21

N;.;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.047

D;.;D;.;.

Sift4G

Benign

0.41

.;.;T;.;T

Polyphen

0.33

B;B;.;B;.

Vest4

0.17

MVP

0.31

MPC

0.85

ClinPred

0.015

GERP RS

4.7

Varity_R

0.13

gMVP

0.095

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