6-30341731-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001369521.2(TRIM39):​c.939T>G​(p.Pro313Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: TRIM39 NM_001369521.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-3.61 with no splicing effect.

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>G	p.Pro313Pro	synonymous	Exon 8 of 8	NP_001356450.1
	TRIM39	NM_021253.4		c.1029T>G	p.Pro343Pro	synonymous	Exon 9 of 9	NP_067076.2
	TRIM39-RPP21	NM_001199119.1		c.939T>G	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>G	p.Pro313Pro	synonymous	Exon 8 of 8	ENSP00000379800.3
	TRIM39	ENST00000396547.5	TSL:1	c.1029T>G	p.Pro343Pro	synonymous	Exon 8 of 8	ENSP00000379796.1
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.939T>G	p.Pro313Pro	synonymous	Exon 7 of 11	ENSP00000485378.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		-3.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;