Variant chr1-33159829-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018207.3(TRIM62):c.620C>T(p.Thr207Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T207T) has been classified as Likely benign.

Frequency

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

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

TRIM62
NM_018207.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

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:

AZIN2 (HGNC:):

AZIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32182705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM62	NM_018207.3 linkuse as main transcript	c.620C>T	p.Thr207Met	missense_variant	3/5	ENST00000291416.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM62	ENST00000291416.10 linkuse as main transcript	c.620C>T	p.Thr207Met	missense_variant	3/5	1	NM_018207.3	P1	Q9BVG3-1
TRIM62	ENST00000543586.1 linkuse as main transcript	c.257C>T	p.Thr86Met	missense_variant	3/5	2			Q9BVG3-2
TRIM62	ENST00000485148.1 linkuse as main transcript	n.669C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250860

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461358

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000656

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 17, 2024

The c.620C>T (p.T207M) alteration is located in exon 3 (coding exon 3) of the TRIM62 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the threonine (T) at amino acid position 207 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.10

Sift

Benign

0.077

T;D

Sift4G

Benign

0.11

T;T

Polyphen

0.97

D;.

Vest4

0.37

MVP

0.67

MPC

1.3

ClinPred

0.21

GERP RS

3.6

Varity_R

0.034

gMVP

0.37

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