rs1116221

Positions:

• chr6-30103553-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007028.5(TRIM31):​c.1261G>A​(p.Glu421Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,612,794 control chromosomes in the GnomAD database, including 62,589 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (6590 hom., cov: 31)
  • Exomes 𝑓: 0.27 (55999 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027345717).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM31	NM_007028.5	c.1261G>A	p.Glu421Lys	missense_variant	9/9	ENST00000376734.4	NP_008959.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM31	ENST00000376734.4	c.1261G>A	p.Glu421Lys	missense_variant	9/9	5	NM_007028.5	ENSP00000365924.3
TRIM31	ENST00000471695.1	n.793G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43416 AN: 151912 Hom.: 6578 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.272

GnomAD3 exomes AF: 0.253 AC: 62466 AN: 246570 Hom.: 8635 AF XY: 0.254 AC XY: 34167 AN XY: 134398

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.0696

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.272 AC: 396761 AN: 1460764 Hom.: 55999 Cov.: 39 AF XY: 0.272 AC XY: 197651 AN XY: 726696

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.0879

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.286 AC: 43467 AN: 152030 Hom.: 6590 Cov.: 31 AF XY: 0.280 AC XY: 20815 AN XY: 74338

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.269

Alfa AF: 0.266 Hom.: 11881

Bravo AF: 0.297

TwinsUK AF: 0.279 AC: 1033

ALSPAC AF: 0.270 AC: 1042

ESP6500AA AF: 0.376 AC: 1136

ESP6500EA AF: 0.261 AC: 1412

ExAC AF: 0.253 AC: 29837

Asia WGS AF: 0.175 AC: 613 AN: 3478

EpiCase AF: 0.269

EpiControl AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Polyphen		0.75	P
Vest4		0.034
MPC		0.40
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.039
gMVP		0.083

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1116221; hg19: chr6-30071330; COSMIC: COSV65060120; COSMIC: COSV65060120;