Variant chr7-73313007-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000333149.7(TRIM50):c.1378G>C(p.Glu460Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,555,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TRIM50
ENST00000333149.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

TRIM50 (HGNC:19017): (tripartite motif containing 50) Enables identical protein binding activity. Predicted to be involved in protein ubiquitination. Predicted to act upstream of or within regulation of establishment of protein localization. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRIM50 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15651819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM50	NM_178125.3 linkuse as main transcript	c.1378G>C	p.Glu460Gln	missense_variant	7/7	ENST00000333149.7	NP_835226.2	Q86XT4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM50	ENST00000333149.7 linkuse as main transcript	c.1378G>C	p.Glu460Gln	missense_variant	7/7	1	NM_178125.3	ENSP00000327994.2		Q86XT4-1
TRIM50	ENST00000453152.1 linkuse as main transcript	c.1378G>C	p.Glu460Gln	missense_variant	7/7	2		ENSP00000413875.1		Q86XT4-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

159924

Hom.:

AF XY:

0.0000236

AC XY:

AN XY:

84628

show subpopulations

Gnomad AFR exome

AF:

0.000219

Gnomad AMR exome

AF:

0.0000801

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1403226

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692464

show subpopulations

Gnomad4 AFR exome

AF:

0.000251

Gnomad4 AMR exome

AF:

0.000111

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:

0.00

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000925

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000263

AC:

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

Mar 12, 2024

The c.1378G>C (p.E460Q) alteration is located in exon 7 (coding exon 6) of the TRIM50 gene. This alteration results from a G to C substitution at nucleotide position 1378, causing the glutamic acid (E) at amino acid position 460 to be replaced by a glutamine (Q). 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

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.65

MutationTaster

Benign

0.83

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.15

Sift

Benign

0.068

T;T

Sift4G

Benign

0.081

T;T

Vest4

0.18

MVP

0.82

MPC

0.87

ClinPred

0.33

GERP RS

4.9

gMVP

0.43

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.

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