6-30108087-A-G

Position:

• chr6-30108087-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007028.5(TRIM31):​c.849T>C​(p.His283His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,596,558 control chromosomes in the GnomAD database, including 318,077 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (32300 hom., cov: 31)
  • Exomes 𝑓: 0.62 (285777 hom.)
• Consequence: TRIM31 NM_007028.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.319 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM31	NM_007028.5	c.849T>C	p.His283His	synonymous_variant	6/9	ENST00000376734.4	NP_008959.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM31	ENST00000376734.4	c.849T>C	p.His283His	synonymous_variant	6/9	5	NM_007028.5	ENSP00000365924.3
TRIM31	ENST00000468264.1	n.113T>C		non_coding_transcript_exon_variant	1/3	3
TRIM31	ENST00000485864.5	n.539T>C		non_coding_transcript_exon_variant	5/6	3
TRIM31-AS1	ENST00000440874.1	n.273+300A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98394 AN: 151814 Hom.: 32281 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.641

GnomAD3 exomes AF: 0.680 AC: 167501 AN: 246282 Hom.: 58159 AF XY: 0.684 AC XY: 91896 AN XY: 134254

Gnomad AFR exome AF: 0.647

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.721

Gnomad EAS exome AF: 0.887

Gnomad SAS exome AF: 0.826

Gnomad FIN exome AF: 0.657

Gnomad NFE exome AF: 0.609

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.623 AC: 900294 AN: 1444626 Hom.: 285777 Cov.: 38 AF XY: 0.630 AC XY: 452997 AN XY: 719466

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.779

Gnomad4 SAS exome AF: 0.825

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.648 AC: 98464 AN: 151932 Hom.: 32300 Cov.: 31 AF XY: 0.656 AC XY: 48753 AN XY: 74262

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.639

Alfa AF: 0.623 Hom.: 59737

Bravo AF: 0.646

Asia WGS AF: 0.811 AC: 2821 AN: 3478

EpiCase AF: 0.607

EpiControl AF: 0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.1
DANN	Benign	0.94

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: rs2023472; hg19: chr6-30075864; COSMIC: COSV65060157; COSMIC: COSV65060157;