Genetic Variant TRIM31:p.Arg72Trp (chr6-30112592-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007028.5(TRIM31):c.214C>T(p.Arg72Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,613,038 control chromosomes in the GnomAD database, including 49 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R72Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 25 hom. )

Consequence

TRIM31
NM_007028.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.150

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033578873).

BP6

Variant 6-30112592-G-A is Benign according to our data. Variant chr6-30112592-G-A is described in ClinVar as Benign. ClinVar VariationId is 776120.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1712/152296) while in subpopulation AFR AF = 0.0343 (1426/41556). AF 95% confidence interval is 0.0328. There are 24 homozygotes in GnomAd4. There are 830 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM31	NM_007028.5 link	c.214C>T	p.Arg72Trp	missense_variant	Exon 2 of 9	ENST00000376734.4	NP_008959.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM31	ENST00000376734.4 link	c.214C>T	p.Arg72Trp	missense_variant	Exon 2 of 9	5	NM_007028.5	ENSP00000365924.3

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1713

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.00343

AC:

846

AN:

246466

AF XY:

0.00277

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.00488

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000967

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00207

AC:

3024

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1324

AN XY:

726684

show subpopulations

African (AFR)

AF:

0.0334

AC:

1119

AN:

33476

American (AMR)

AF:

0.00566

AC:

253

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000268

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000255

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52314

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00126

AC:

1401

AN:

1111996

Other (OTH)

AF:

0.00346

AC:

209

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

190

379

569

758

948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0112

AC:

1712

AN:

152296

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

830

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0343

AC:

1426

AN:

41556

American (AMR)

AF:

0.0109

AC:

167

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

68038

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00461

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0334

AC:

101

ESP6500EA

AF:

0.000369

AC:

ExAC

AF:

0.00383

AC:

451

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.082

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.0

PhyloP100

-0.15

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.5

REVEL

Benign

0.26

Sift

Benign

0.034

Sift4G

Uncertain

0.023

Vest4

0.076

ClinPred

0.044

GERP RS

-3.1

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.073

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over