NM_001369521.2:c.1345C>T

Variant names:

• chr6-30342137-C-T
• NM_001369521.2:c.1345C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369521.2(TRIM39):​c.1345C>T​(p.His449Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM39 NM_001369521.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM39	NM_001369521.2	MANE Select	c.1345C>T	p.His449Tyr	missense	Exon 8 of 8	NP_001356450.1	Q9HCM9-2
	TRIM39	NM_021253.4		c.1435C>T	p.His479Tyr	missense	Exon 9 of 9	NP_067076.2
	TRIM39	NM_001369522.1		c.1345C>T	p.His449Tyr	missense	Exon 8 of 8	NP_001356451.1	Q9HCM9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM39	ENST00000396551.9	TSL:5 MANE Select	c.1345C>T	p.His449Tyr	missense	Exon 8 of 8	ENSP00000379800.3	Q9HCM9-2
	TRIM39	ENST00000396547.5	TSL:1	c.1435C>T	p.His479Tyr	missense	Exon 8 of 8	ENSP00000379796.1	Q9HCM9-1
	TRIM39	ENST00000376659.9	TSL:1	c.1345C>T	p.His449Tyr	missense	Exon 8 of 8	ENSP00000365847.5	Q9HCM9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.4
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.021	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.68		Loss of sheet (P = 0.1158)
MVP		0.74
MPC		3.0
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.18
gMVP		0.95
Mutation Taster		=75/25	polymorphism

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

hg19: chr6-30309914;