6-30110667-T-G

Position:

chr6-30110667-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_007028.5(TRIM31):c.525A>C(p.Glu175Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,614,158 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 37 hom. )

Consequence

TRIM31
NM_007028.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

TRIM31 (HGNC:16289): (tripartite motif containing 31) This gene encodes a protein that functions as an E3 ubiquitin-protein ligase. This gene shows altered expression in certain tumors and may be a negative regulator of cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TRIM31 links:

TRIM31 (HGNC:):

TRIM31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047485232).

BP6

Variant 6-30110667-T-G is Benign according to our data. Variant chr6-30110667-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 782822.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM31	NM_007028.5 linkuse as main transcript	c.525A>C	p.Glu175Asp	missense_variant	4/9	ENST00000376734.4	NP_008959.3	Q9BZY9-1Q2L6J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM31	ENST00000376734.4 linkuse as main transcript	c.525A>C	p.Glu175Asp	missense_variant	4/9	5	NM_007028.5	ENSP00000365924.3	Q9BZY9-1
TRIM31	ENST00000480808.1 linkuse as main transcript	n.71A>C		non_coding_transcript_exon_variant	2/3	3
TRIM31	ENST00000485864.5 linkuse as main transcript	n.215A>C		non_coding_transcript_exon_variant	3/6	3
TRIM31-AS1	ENST00000440874.1 linkuse as main transcript	n.274-1051T>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000235

AC:

AN:

251452

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00201

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000288

AC:

421

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

181

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.000328

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.000576

Hom.:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.525A>C (p.E175D) alteration is located in exon 4 (coding exon 3) of the TRIM31 gene. This alteration results from a A to C substitution at nucleotide position 525, causing the glutamic acid (E) at amino acid position 175 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.30

DANN

Benign

0.89

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0090

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

REVEL

Benign

0.19

Sift

Benign

0.21

Sift4G

Benign

0.42

Polyphen

0.052

Vest4

0.047

MutPred

0.29

Gain of ubiquitination at K178 (P = 0.1092);

MVP

0.34

MPC

0.23

ClinPred

0.031

GERP RS

-7.0

Varity_R

0.023

gMVP

0.059

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