6-30103586-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_007028.5(TRIM31):c.1228G>T(p.Glu410Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,613,104 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0050 (25 hom.)
• Consequence: TRIM31 NM_007028.5 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.261

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_007028.5 Downstream stopcodon found after 9 codons.
• BP6: Variant 6-30103586-C-A is Benign according to our data. Variant chr6-30103586-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 710431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.1228G>T	p.Glu410Ter	stop_gained	9/9	ENST00000376734.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.1228G>T	p.Glu410Ter	stop_gained	9/9	5	NM_007028.5	P1
TRIM31	ENST00000471695.1	n.760G>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 508 AN: 152200 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00391 AC: 965 AN: 246644 Hom.: 5 AF XY: 0.00371 AC XY: 499 AN XY: 134438

Gnomad AFR exome AF: 0.000927

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00485

Gnomad NFE exome AF: 0.00725

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00499 AC: 7293 AN: 1460786 Hom.: 25 Cov.: 33 AF XY: 0.00490 AC XY: 3561 AN XY: 726708

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.000715

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.00603

Gnomad4 OTH exome AF: 0.00374

GnomAD4 genome AF: 0.00333 AC: 507 AN: 152318 Hom.: 3 Cov.: 31 AF XY: 0.00330 AC XY: 246 AN XY: 74480

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00495 Hom.: 4

Bravo AF: 0.00287

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.000993 AC: 3

ESP6500EA AF: 0.00498 AC: 27

ExAC AF: 0.00467 AC: 553

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00539

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Pathogenic	0.29
Cadd	Pathogenic	34
Dann	Benign	0.93
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.013	N
MutationTaster	Benign	0.62	A;N
Vest4		0.026
GERP RS		-0.41

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

Other links and lift over

dbSNP: rs146885411; hg19: chr6-30071363;