Variant 6-127287180-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001242850.2(RNF146):c.567C>T(p.Thr189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,613,216 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 1 hom. )

Consequence

RNF146
NM_001242850.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.823

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-127287180-C-T is Benign according to our data. Variant chr6-127287180-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656899.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.823 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF146	NM_001242850.2 linkuse as main transcript	c.567C>T	p.Thr189=	synonymous_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.567C>T	p.Thr189=	synonymous_variant	3/3	2	NM_001242850.2	ENSP00000357297	A1	Q9NTX7-1
RNF146	ENST00000610153.1 linkuse as main transcript	c.567C>T	p.Thr189=	synonymous_variant	3/3	2		ENSP00000476814	A1	Q9NTX7-1
RNF146	ENST00000608991.5 linkuse as main transcript	c.564C>T	p.Thr188=	synonymous_variant	5/5	4		ENSP00000477168	P4	Q9NTX7-2
RNF146	ENST00000356799.6 linkuse as main transcript	c.*572C>T		3_prime_UTR_variant	4/4	2		ENSP00000349253

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00112

AC:

280

AN:

250188

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.00175

AC:

2558

AN:

1461260

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1253

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00218

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

151956

Hom.:

Cov.:

AF XY:

0.000929

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00119

EpiCase

AF:

0.00180

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

RNF146: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

DANN

Benign

0.76

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