13-50012478-G-C

Variant names:

• chr13-50012478-G-C
• NM_213590.3:c.538G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_213590.3(TRIM13):​c.538G>C​(p.Asp180His) 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 benign 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: 7.65

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36880434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM13	NM_213590.3	c.538G>C	p.Asp180His	missense_variant	Exon 2 of 2	ENST00000378182.4	NP_998755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM13	ENST00000378182.4	c.538G>C	p.Asp180His	missense_variant	Exon 2 of 2	1	NM_213590.3	ENSP00000367424.3

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

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547G>C (p.D183H) alteration is located in exon 4 (coding exon 2) of the TRIM13 gene. This alteration results from a G to C substitution at nucleotide position 547, causing the aspartic acid (D) at amino acid position 183 to be replaced by a histidine (H). 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	Benign	0.31
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;T;T;.;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;.;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;L;.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		1.0	.;D;D;D;D
Vest4		0.42, 0.39, 0.43, 0.44
MutPred		0.35		Loss of ubiquitination at K177 (P = 0.0352);Loss of ubiquitination at K177 (P = 0.0352);Loss of ubiquitination at K177 (P = 0.0352);.;Loss of ubiquitination at K177 (P = 0.0352);
MVP		0.34
MPC		0.56
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.66

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: chr13-50586614;