chr6-30108126-C-T

Variant names:

• chr6-30108126-C-T
• rs28400887
• NM_007028.5:c.810G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_Moderate BA1

The NM_007028.5(TRIM31):​c.810G>A​(p.Leu270Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,604,824 control chromosomes in the GnomAD database, including 48,960 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 0.25 (5077 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43883 hom.)
• Consequence: TRIM31 NM_007028.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 20 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM31	NM_007028.5	MANE Select	c.810G>A	p.Leu270Leu	synonymous	Exon 6 of 9	NP_008959.3
	TRIM31	NR_134870.2		n.920G>A		non_coding_transcript_exon	Exon 6 of 10
	TRIM31-AS1	NR_126470.1		n.273+339C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM31	ENST00000376734.4	TSL:5 MANE Select	c.810G>A	p.Leu270Leu	synonymous	Exon 6 of 9	ENSP00000365924.3
	TRIM31	ENST00000468264.1	TSL:3	n.74G>A		non_coding_transcript_exon	Exon 1 of 3
	TRIM31	ENST00000485864.5	TSL:3	n.500G>A		non_coding_transcript_exon	Exon 5 of 6

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38484 AN: 151926 Hom.: 5070 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.257 AC: 63229 AN: 246390 AF XY: 0.246

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.240 AC: 348050 AN: 1452776 Hom.: 43883 Cov.: 37 AF XY: 0.236 AC XY: 170766 AN XY: 723140

African (AFR) AF: 0.246 AC: 8194 AN: 33298

American (AMR) AF: 0.345 AC: 15410 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3796 AN: 26106

East Asian (EAS) AF: 0.225 AC: 8923 AN: 39664

South Asian (SAS) AF: 0.160 AC: 13803 AN: 86140

European-Finnish (FIN) AF: 0.306 AC: 15981 AN: 52250

Middle Eastern (MID) AF: 0.169 AC: 972 AN: 5756

European-Non Finnish (NFE) AF: 0.242 AC: 267543 AN: 1104784

Other (OTH) AF: 0.223 AC: 13428 AN: 60094

GnomAD4 genome AF: 0.253 AC: 38523 AN: 152048 Hom.: 5077 Cov.: 32 AF XY: 0.254 AC XY: 18916 AN XY: 74348

African (AFR) AF: 0.250 AC: 10369 AN: 41438

American (AMR) AF: 0.303 AC: 4638 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5166

South Asian (SAS) AF: 0.183 AC: 881 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3275 AN: 10578

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16773 AN: 67978

Other (OTH) AF: 0.209 AC: 440 AN: 2110

Alfa AF: 0.241 Hom.: 13579

Bravo AF: 0.253

Asia WGS AF: 0.183 AC: 637 AN: 3478

EpiCase AF: 0.226

EpiControl AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	17
DANN	Benign	0.52
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.83		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.83		Position offset: -2
DS_AL_spliceai		0.35		Position offset: 42

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28400887; hg19: chr6-30075903; COSMIC: COSV65060295; COSMIC: COSV65060295;