Variant chr11-5611325-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001003818.3(TRIM6):c.1534C>T(p.Arg512Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,216 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

TRIM6
NM_001003818.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0890

Variant links:

Genes affected

TRIM6 (HGNC:16277): (tripartite motif containing 6) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, B-box type 1 and B-box type 2 domain, and a coiled-coil region. The protein localizes to the nucleus, but its specific function has not been identified. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from this gene into the downstream TRIM34 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

TRIM6 links:

TRIM6-TRIM34 (HGNC:):

TRIM6-TRIM34 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008818895).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM6	NM_001003818.3 linkuse as main transcript	c.1534C>T	p.Arg512Cys	missense_variant	8/8	ENST00000380097.8
TRIM6-TRIM34	NM_001003819.4 linkuse as main transcript	c.985+764C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM6	ENST00000380097.8 linkuse as main transcript	c.1534C>T	p.Arg512Cys	missense_variant	8/8	1	NM_001003818.3		Q9C030-2

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

191

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000821

AC:

206

AN:

250922

Hom.:

AF XY:

0.000789

AC XY:

107

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.00175

AC:

2561

AN:

1461030

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1178

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000843

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00126

AC:

191

AN:

152186

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00127

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.000807

AC:

EpiCase

AF:

0.00174

EpiControl

AF:

0.00166

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

Aug 30, 2021

The c.1534C>T (p.R512C) alteration is located in exon 8 (coding exon 8) of the TRIM6 gene. This alteration results from a C to T substitution at nucleotide position 1534, causing the arginine (R) at amino acid position 512 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.0016

T;.;.;.;.;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

D;.;.;D;.;.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.0088

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

N;.;.;.;.;.;.;.

MutationTaster

Benign

0.89

N;N;N;N;N;N;N;N;N;N

PROVEAN

Benign

6.8

N;N;N;N;N;N;N;.

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.028

B;.;B;B;.;.;.;B

Vest4

0.19

MVP

0.25

MPC

0.031

ClinPred

0.0078

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.076

gMVP

0.32

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