6-30342137-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

Scores

5
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM39NM_001369521.2 linkc.1345C>T p.His449Tyr missense_variant Exon 8 of 8 ENST00000396551.9 NP_001356450.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM39ENST00000396551.9 linkc.1345C>T p.His449Tyr missense_variant Exon 8 of 8 5 NM_001369521.2 ENSP00000379800.3 Q9HCM9-2
TRIM39-RPP21ENST00000623385.3 linkc.1104+241C>T intron_variant Intron 7 of 10 5 ENSP00000485378.1 A0A096LP39

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1435C>T (p.H479Y) alteration is located in exon 9 (coding exon 7) of the TRIM39 gene. This alteration results from a C to T substitution at nucleotide position 1435, causing the histidine (H) at amino acid position 479 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;.;.;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;D;D;D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Pathogenic
3.4
M;.;.;.;M
PROVEAN
Uncertain
-3.1
D;D;D;D;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.021
D;T;T;T;D
Sift4G
Benign
0.10
T;T;T;T;T
Polyphen
1.0
D;D;D;D;D
Vest4
0.40
MutPred
0.68
Loss of sheet (P = 0.1158);.;.;.;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30309914; API