6-30341731-T-C

Variant names:

• chr6-30341731-T-C
• rs2074474
• NM_001369521.2:c.939T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001369521.2(TRIM39):​c.939T>C​(p.Pro313Pro) 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
• Publications: 32 publications found

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:38845): (TRIM39-RPP21 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TRIM39 (tripartite motif-containing 39) and RPP21 (ribonuclease P/MRP 21kDa subunit) genes on chromosome 6. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369521.2. 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
	TRIM39	NM_001369521.2	MANE Select	c.939T>C	p.Pro313Pro	synonymous	Exon 8 of 8	NP_001356450.1
	TRIM39	NM_021253.4		c.1029T>C	p.Pro343Pro	synonymous	Exon 9 of 9	NP_067076.2
	TRIM39-RPP21	NM_001199119.1		c.939T>C	p.Pro313Pro	synonymous	Exon 6 of 10	NP_001186048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM39	ENST00000396551.9	TSL:5 MANE Select	c.939T>C	p.Pro313Pro	synonymous	Exon 8 of 8	ENSP00000379800.3
	TRIM39	ENST00000396547.5	TSL:1	c.1029T>C	p.Pro343Pro	synonymous	Exon 8 of 8	ENSP00000379796.1
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.939T>C	p.Pro313Pro	synonymous	Exon 7 of 11	ENSP00000485378.1

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

GnomAD2 exomes AF: 0.306 AC: 74939 AN: 244764 AF XY: 0.300

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 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

African (AFR) AF: 0.294 AC: 9823 AN: 33464

American (AMR) AF: 0.458 AC: 20412 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 9458 AN: 26034

East Asian (EAS) AF: 0.526 AC: 20865 AN: 39686

South Asian (SAS) AF: 0.347 AC: 29906 AN: 86148

European-Finnish (FIN) AF: 0.264 AC: 13786 AN: 52192

Middle Eastern (MID) AF: 0.282 AC: 1628 AN: 5766

European-Non Finnish (NFE) AF: 0.217 AC: 241708 AN: 1111442

Other (OTH) AF: 0.276 AC: 16627 AN: 60342

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

African (AFR) AF: 0.292 AC: 12110 AN: 41478

American (AMR) AF: 0.390 AC: 5957 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1330 AN: 3466

East Asian (EAS) AF: 0.484 AC: 2489 AN: 5140

South Asian (SAS) AF: 0.394 AC: 1896 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2887 AN: 10574

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15190 AN: 67952

Other (OTH) AF: 0.311 AC: 657 AN: 2112

Alfa AF: 0.253 Hom.: 19678

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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