chr13-50012858-C-A

Variant names:

• chr13-50012858-C-A
• rs766584514
• NM_213590.3:c.918C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213590.3(TRIM13):​c.918C>A​(p.Phe306Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM13 NM_213590.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213590.3. 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
	TRIM13	NM_213590.3	MANE Select	c.918C>A	p.Phe306Leu	missense	Exon 2 of 2	NP_998755.1	O60858-1
	TRIM13	NM_001007278.3		c.927C>A	p.Phe309Leu	missense	Exon 4 of 4	NP_001007279.1	O60858-3
	TRIM13	NM_005798.5		c.918C>A	p.Phe306Leu	missense	Exon 3 of 3	NP_005789.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM13	ENST00000378182.4	TSL:1 MANE Select	c.918C>A	p.Phe306Leu	missense	Exon 2 of 2	ENSP00000367424.3	O60858-1
	TRIM13	ENST00000356017.8	TSL:1	c.927C>A	p.Phe309Leu	missense	Exon 4 of 4	ENSP00000348299.4	O60858-3
	TRIM13	ENST00000420995.6	TSL:1	c.918C>A	p.Phe306Leu	missense	Exon 3 of 3	ENSP00000412943.2	O60858-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727216

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.67
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.038
Sift	Benign	0.42	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.011
MutPred		0.47		Loss of helix (P = 0.0017)
MVP		0.13
MPC		0.12
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.054
gMVP		0.32
Mutation Taster		=90/10	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

dbSNP: rs766584514; hg19: chr13-50586994;