6-30110458-T-C

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.734A>G(p.Gln245Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,614,156 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. Q245P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0080 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (18 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510

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=0.007272631).
• BP6: Variant 6-30110458-T-C is Benign according to our data. Variant chr6-30110458-T-C is described in ClinVar as [Benign]. Clinvar id is 768071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00805 (1226/152308) while in subpopulation AFR AF= 0.0256 (1064/41556). AF 95% confidence interval is 0.0243. There are 8 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.734A>G	p.Gln245Arg	missense_variant	4/9	ENST00000376734.4
TRIM31-AS1	NR_126470.1	n.274-1260T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.734A>G	p.Gln245Arg	missense_variant	4/9	5	NM_007028.5	P1
TRIM31-AS1	ENST00000440874.1	n.274-1260T>C		intron_variant, non_coding_transcript_variant		3
TRIM31	ENST00000480808.1	n.280A>G		non_coding_transcript_exon_variant	2/3	3
TRIM31	ENST00000485864.5	n.424A>G		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1221 AN: 152190 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00247 AC: 622 AN: 251418 Hom.: 8 AF XY: 0.00200 AC XY: 272 AN XY: 135880

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.00390

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000448

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000967 AC: 1414 AN: 1461848 Hom.: 18 Cov.: 31 AF XY: 0.000877 AC XY: 638 AN XY: 727218

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.00423

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00805 AC: 1226 AN: 152308 Hom.: 8 Cov.: 32 AF XY: 0.00801 AC XY: 597 AN XY: 74488

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.000699 Hom.: 0

Bravo AF: 0.00974

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00279 AC: 339

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000948

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

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	14
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.038	N
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.015
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.034	B
Vest4		0.067
MVP		0.58
MPC		0.26
ClinPred		0.012	T
GERP RS		0.95
Varity_R		0.022
gMVP		0.036

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: rs138900010; hg19: chr6-30078235; COSMIC: COSV105310238; COSMIC: COSV105310238;