Variant 1-33165493-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018207.3(TRIM62):c.482A>G(p.Lys161Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,608,090 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TRIM62
NM_018207.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

Variant links:

Genes affected

TRIM62 (HGNC:25574): (tripartite motif containing 62) Enables identical protein binding activity; transcription coactivator activity; and ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of viral transcription; positive regulation of NF-kappaB transcription factor activity; and positive regulation of antifungal innate immune response. Is active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM62 links:

(HGNC:):

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=0.13179395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRIM62	NM_018207.3 linkuse as main transcript	c.482A>G	p.Lys161Arg	missense_variant	2/5	ENST00000291416.10
TRIM62	NM_001330483.2 linkuse as main transcript	c.119A>G	p.Lys40Arg	missense_variant	2/5
AZIN2	XM_047443457.1 linkuse as main transcript	c.*4528T>C		3_prime_UTR_variant	10/10
ZNF362	XM_047447108.1 linkuse as main transcript	c.-24+37044T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM62	ENST00000291416.10 linkuse as main transcript	c.482A>G	p.Lys161Arg	missense_variant	2/5	1	NM_018207.3	P1	Q9BVG3-1
	ENST00000624339.1 linkuse as main transcript	n.2643T>C		non_coding_transcript_exon_variant	1/1
TRIM62	ENST00000543586.1 linkuse as main transcript	c.119A>G	p.Lys40Arg	missense_variant	2/5	2			Q9BVG3-2
TRIM62	ENST00000485148.1 linkuse as main transcript	n.531A>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242446

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

131012

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.00

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:

0.00000893

AC:

AN:

1455884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723714

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000165

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

Jun 22, 2023

The c.482A>G (p.K161R) alteration is located in exon 2 (coding exon 2) of the TRIM62 gene. This alteration results from a A to G substitution at nucleotide position 482, causing the lysine (K) at amino acid position 161 to be replaced by an arginine (R). 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

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.063

Sift

Benign

0.50

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.22

B;.

Vest4

0.21

MutPred

0.33

Loss of ubiquitination at K161 (P = 0.0098);.;

MVP

0.65

MPC

0.58

ClinPred

0.16

GERP RS

4.9

Varity_R

0.19

gMVP

0.32

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