13-50012581-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_213590.3(TRIM13):​c.641C>T​(p.Ala214Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TRIM13
NM_213590.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14550263).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIM13NM_213590.3 linkuse as main transcriptc.641C>T p.Ala214Val missense_variant 2/2 ENST00000378182.4 NP_998755.1
DLEU2NR_152566.1 linkuse as main transcriptn.1314+14626G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIM13ENST00000378182.4 linkuse as main transcriptc.641C>T p.Ala214Val missense_variant 2/21 NM_213590.3 ENSP00000367424 P4O60858-1
DLEU2ENST00000621282.4 linkuse as main transcriptn.1314+14626G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
16
AN:
250844
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135628
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461806
Hom.:
0
Cov.:
33
AF XY:
0.0000206
AC XY:
15
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000402
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 18, 2022The c.650C>T (p.A217V) alteration is located in exon 4 (coding exon 2) of the TRIM13 gene. This alteration results from a C to T substitution at nucleotide position 650, causing the alanine (A) at amino acid position 217 to be replaced by a valine (V). 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
0.21
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.45
CADD
Uncertain
24
DANN
Benign
0.89
DEOGEN2
Benign
0.026
T;T;T;.;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.92
D;.;.;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L;L;.;L
MutationTaster
Benign
0.81
D;D;D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.1
N;N;N;N;N
REVEL
Benign
0.065
Sift
Benign
0.27
T;T;T;T;T
Sift4G
Benign
0.82
T;T;T;T;T
Polyphen
0.30, 0.42
.;B;B;B;B
Vest4
0.36, 0.30, 0.35, 0.36
MutPred
0.37
Gain of phosphorylation at Y215 (P = 0.3929);Gain of phosphorylation at Y215 (P = 0.3929);Gain of phosphorylation at Y215 (P = 0.3929);.;Gain of phosphorylation at Y215 (P = 0.3929);
MVP
0.21
MPC
0.28
ClinPred
0.13
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770375706; hg19: chr13-50586717; API