6-30110488-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007028.5(TRIM31):c.704T>C(p.Leu235Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00291 in 1,614,140 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.011 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (24 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.14

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053934157).
• BP6: Variant 6-30110488-A-G is Benign according to our data. Variant chr6-30110488-A-G is described in ClinVar as [Benign]. Clinvar id is 776117.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 (1711/152248) while in subpopulation AFR AF= 0.0344 (1428/41528). AF 95% confidence interval is 0.0329. There are 25 homozygotes in gnomad4. There are 829 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.704T>C	p.Leu235Pro	missense_variant	4/9	ENST00000376734.4
TRIM31-AS1	NR_126470.1	n.274-1230A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.704T>C	p.Leu235Pro	missense_variant	4/9	5	NM_007028.5	P1
TRIM31-AS1	ENST00000440874.1	n.274-1230A>G		intron_variant, non_coding_transcript_variant		3
TRIM31	ENST00000480808.1	n.250T>C		non_coding_transcript_exon_variant	2/3	3
TRIM31	ENST00000485864.5	n.394T>C		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1712 AN: 152130 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00350 AC: 879 AN: 251486 Hom.: 6 AF XY: 0.00282 AC XY: 383 AN XY: 135920

Gnomad AFR exome AF: 0.0359

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000949

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00205 AC: 2990 AN: 1461892 Hom.: 24 Cov.: 31 AF XY: 0.00180 AC XY: 1307 AN XY: 727248

Gnomad4 AFR exome AF: 0.0335

Gnomad4 AMR exome AF: 0.00566

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.0112 AC: 1711 AN: 152248 Hom.: 25 Cov.: 32 AF XY: 0.0111 AC XY: 829 AN XY: 74452

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00993 Hom.: 843

Bravo AF: 0.0131

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0304 AC: 134

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00398 AC: 483

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.13
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.26	N
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.76
MPC		1.1
ClinPred		0.090	T
GERP RS		2.9
Varity_R		0.30
gMVP		0.45

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: rs35775852; hg19: chr6-30078265;