13-50012289-T-G

Position:

• chr13-50012289-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_213590.3(TRIM13):​c.349T>G​(p.Cys117Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM13 NM_213590.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99

Genes affected

TRIM13 (HGNC:9976): (tripartite motif containing 13) This gene encodes 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. This gene is located on chromosome 13 within the minimal deletion region for B-cell chronic lymphocytic leukemia. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

DLEU2 (HGNC:13748): (deleted in lymphocytic leukemia 2) This locus represents a microRNA host gene and also produces long alternatively spliced non-coding RNAs. This genome region was observed to be deleted or epigenetically suppressed in leukemia, and was implicated as a negative regulator of cell proliferation. However, an alternative transcript produced at this locus was also found to promote progression through the cell cycle via angiotensin I converting enzyme 2 and cyclin D1. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity TRI13_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.991

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM13	NM_213590.3	c.349T>G	p.Cys117Gly	missense_variant	2/2	ENST00000378182.4	NP_998755.1
DLEU2	NR_152566.1	n.1315-14870A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM13	ENST00000378182.4	c.349T>G	p.Cys117Gly	missense_variant	2/2	1	NM_213590.3	ENSP00000367424	P4
DLEU2	ENST00000621282.4	n.1315-14870A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.358T>G (p.C120G) alteration is located in exon 4 (coding exon 2) of the TRIM13 gene. This alteration results from a T to G substitution at nucleotide position 358, causing the cysteine (C) at amino acid position 120 to be replaced by a glycine (G). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	.;T;T;T;.;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;.;.;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.3	.;.;H;H;.;H
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-12	D;D;D;D;D;D
REVEL	Pathogenic	0.98
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;.;D;D;D;D
Vest4		0.96, 0.96, 0.98, 0.98
MutPred		0.95		Gain of disorder (P = 0.0282);Gain of disorder (P = 0.0282);Gain of disorder (P = 0.0282);Gain of disorder (P = 0.0282);.;Gain of disorder (P = 0.0282);
MVP		0.99
MPC		0.59
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.94

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: chr13-50586425;