Variant 1-114421576-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000358465.7(TRIM33):c.1921A>G(p.Asn641Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRIM33
ENST00000358465.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

TRIM33 (HGNC:16290): (tripartite motif containing 33) The protein encoded by this gene is thought to be a transcriptional corepressor. However, molecules that interact with this protein have not yet been identified. The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. [provided by RefSeq, Jul 2008]

TRIM33 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM33	NM_015906.4 linkuse as main transcript	c.1921A>G	p.Asn641Asp	missense_variant	11/20	ENST00000358465.7	NP_056990.3	Q9UPN9-1B3KN30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM33	ENST00000358465.7 linkuse as main transcript	c.1921A>G	p.Asn641Asp	missense_variant	11/20	1	NM_015906.4	ENSP00000351250.2	Q9UPN9-1
TRIM33	ENST00000369543.6 linkuse as main transcript	c.1921A>G	p.Asn641Asp	missense_variant	11/19	1		ENSP00000358556.2	Q9UPN9-2
TRIM33	ENST00000448034.5 linkuse as main transcript	c.1129A>G	p.Asn377Asp	missense_variant	8/18	5		ENSP00000402333.1	H0Y612

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 12, 2024

The c.1921A>G (p.N641D) alteration is located in exon 11 (coding exon 11) of the TRIM33 gene. This alteration results from a A to G substitution at nucleotide position 1921, causing the asparagine (N) at amino acid position 641 to be replaced by an aspartic acid (D). 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

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.080

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.14

T;T

Polyphen

1.0

D;D

Vest4

0.80

MutPred

0.23

Gain of phosphorylation at T639 (P = 0.1064);Gain of phosphorylation at T639 (P = 0.1064);

MVP

0.40

MPC

0.84

ClinPred

0.71

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over