Variant 6-30196718-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003449.5(TRIM26):c.563T>C(p.Ile188Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

TRIM26
NM_003449.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.49

Variant links:

Genes affected

TRIM26 (HGNC:12962): (tripartite motif containing 26) 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 protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2011]

TRIM26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05420983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM26	NM_003449.5 linkuse as main transcript	c.563T>C	p.Ile188Thr	missense_variant	6/10	ENST00000454678.7	NP_003440.1	Q12899A0A024RCP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM26	ENST00000454678.7 linkuse as main transcript	c.563T>C	p.Ile188Thr	missense_variant	6/10	1	NM_003449.5	ENSP00000410446.2	Q12899
TRIM26	ENST00000437089.5 linkuse as main transcript	c.563T>C	p.Ile188Thr	missense_variant	5/9	1		ENSP00000395491.1	Q12899
TRIM26	ENST00000453195.5 linkuse as main transcript	c.563T>C	p.Ile188Thr	missense_variant	5/9	1		ENSP00000391879.1	Q12899
TRIM26	ENST00000416596.5 linkuse as main transcript	c.563T>C	p.Ile188Thr	missense_variant	6/6	5		ENSP00000413673.1	A2AE48

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

250604

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000118

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.563T>C (p.I188T) alteration is located in exon 6 (coding exon 3) of the TRIM26 gene. This alteration results from a T to C substitution at nucleotide position 563, causing the isoleucine (I) at amino acid position 188 to be replaced by a threonine (T). 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

0.30

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.074

T;T;T;T

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

.;.;T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.054

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.4

L;L;L;.

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D;D;N

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D;D;T

Sift4G

Benign

0.070

T;T;T;.

Polyphen

0.37

B;B;B;.

Vest4

0.83

MutPred

0.58

Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);Gain of disorder (P = 0.0499);

MVP

0.92

MPC

1.1

ClinPred

0.16

GERP RS

5.4

Varity_R

0.092

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over