Variant 7-73313300-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178125.3(TRIM50):c.1085G>A(p.Arg362His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000669 in 1,605,486 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 5 hom. )

Consequence

TRIM50
NM_178125.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.888

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0390805).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM50	NM_178125.3 linkuse as main transcript	c.1085G>A	p.Arg362His	missense_variant	7/7	ENST00000333149.7	NP_835226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM50	ENST00000333149.7 linkuse as main transcript	c.1085G>A	p.Arg362His	missense_variant	7/7	1	NM_178125.3	ENSP00000327994	P1	Q86XT4-1
TRIM50	ENST00000453152.1 linkuse as main transcript	c.1085G>A	p.Arg362His	missense_variant	7/7	2		ENSP00000413875	P1	Q86XT4-1
TRIM50	ENST00000488217.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000750

AC:

114

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000680

AC:

157

AN:

231022

Hom.:

AF XY:

0.000684

AC XY:

AN XY:

125750

show subpopulations

Gnomad AFR exome

AF:

0.0000717

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.000671

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000661

AC:

960

AN:

1453276

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

515

AN XY:

722238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000460

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.000805

Gnomad4 OTH exome

AF:

0.000417

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152210

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000785

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

Apr 29, 2024

The c.1085G>A (p.R362H) alteration is located in exon 7 (coding exon 6) of the TRIM50 gene. This alteration results from a G to A substitution at nucleotide position 1085, causing the arginine (R) at amino acid position 362 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.095

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.63

MutationTaster

Benign

0.71

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.063

T;T

Sift4G

Benign

0.24

T;T

Vest4

0.43

MVP

0.78

MPC

1.0

ClinPred

0.089

GERP RS

3.7

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

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