rs2074474

chr6-30341731-T-C

Variant summary

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

The NM_001369521.2(TRIM39):c.939T>C(p.Pro313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,611,674 control chromosomes in the GnomAD database, including 56,734 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 0.28 (6480 hom., cov: 31)
  • Exomes 𝑓: 0.25 (50254 hom.)
• Consequence: TRIM39 NM_001369521.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61

Genes affected

TRIM39 (HGNC:10065): (tripartite motif containing 39) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The function of this protein has not been identified. This gene lies within the major histocompatibility complex class I region on chromosome 6. Alternate splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TRIM39-RPP21 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-3.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM39	NM_001369521.2	c.939T>C	p.Pro313=	synonymous_variant	8/8	ENST00000396551.9
TRIM39-RPP21	NM_001199119.1	c.939T>C	p.Pro313=	synonymous_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM39	ENST00000396551.9	c.939T>C	p.Pro313=	synonymous_variant	8/8	5	NM_001369521.2	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42870 AN: 151908 Hom.: 6470 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.309

GnomAD3 exomes AF: 0.306 AC: 74939 AN: 244764 Hom.: 12773 AF XY: 0.300 AC XY: 40062 AN XY: 133466

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.455

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.250 AC: 364213 AN: 1459648 Hom.: 50254 Cov.: 34 AF XY: 0.251 AC XY: 182511 AN XY: 726084

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.526

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.282 AC: 42923 AN: 152026 Hom.: 6480 Cov.: 31 AF XY: 0.287 AC XY: 21329 AN XY: 74300

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.311

Alfa AF: 0.252 Hom.: 8698

Bravo AF: 0.293

Asia WGS AF: 0.444 AC: 1544 AN: 3478

EpiCase AF: 0.242

EpiControl AF: 0.246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.9
Dann	Benign	0.60

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: rs2074474; hg19: chr6-30309508; COSMIC: COSV64955383; COSMIC: COSV64955383;