Genetic Variant TRIM31:p.Asp284Asn (chr6-30108086-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007028.5(TRIM31):c.850G>A(p.Asp284Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,609,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TRIM31
NM_007028.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.675

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-AS1 (HGNC:39761): (TRIM31 antisense RNA 1)

TRIM31-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03377229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM31	NM_007028.5 link	c.850G>A	p.Asp284Asn	missense_variant	Exon 6 of 9	ENST00000376734.4	NP_008959.3	Q9BZY9-1Q2L6J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM31	ENST00000376734.4 link	c.850G>A	p.Asp284Asn	missense_variant	Exon 6 of 9	5	NM_007028.5	ENSP00000365924.3	Q9BZY9-1
TRIM31	ENST00000468264.1 link	n.114G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
TRIM31	ENST00000485864.5 link	n.540G>A		non_coding_transcript_exon_variant	Exon 5 of 6	3
TRIM31-AS1	ENST00000440874.1 link	n.273+299C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246564

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1457520

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000339

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.850G>A (p.D284N) alteration is located in exon 6 (coding exon 5) of the TRIM31 gene. This alteration results from a G to A substitution at nucleotide position 850, causing the aspartic acid (D) at amino acid position 284 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.9

DANN

Benign

0.93

DEOGEN2

Benign

0.00093

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.0042

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.62

REVEL

Benign

0.077

Sift

Benign

0.55

Sift4G

Benign

0.097

Polyphen

0.67

Vest4

0.069

MutPred

0.32

Gain of MoRF binding (P = 0.0399);

MVP

0.48

MPC

0.25

ClinPred

0.14

GERP RS

1.2

Varity_R

0.060

gMVP

0.027

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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