Genetic Variant TRIM33:p.Gly607Ser (chr1-114424632-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015906.4(TRIM33):c.1819G>A(p.Gly607Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000282 in 1,456,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

TRIM33
NM_015906.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.26

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08149487).

BS2

High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM33	NM_015906.4 link	c.1819G>A	p.Gly607Ser	missense_variant	Exon 10 of 20	ENST00000358465.7	NP_056990.3	Q9UPN9-1B3KN30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM33	ENST00000358465.7 link	c.1819G>A	p.Gly607Ser	missense_variant	Exon 10 of 20	1	NM_015906.4	ENSP00000351250.2	Q9UPN9-1
TRIM33	ENST00000369543.6 link	c.1819G>A	p.Gly607Ser	missense_variant	Exon 10 of 19	1		ENSP00000358556.2	Q9UPN9-2
TRIM33	ENST00000448034.5 link	c.1027G>A	p.Gly343Ser	missense_variant	Exon 7 of 18	5		ENSP00000402333.1	H0Y612

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000565

AC:

AN:

247882

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134094

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:

0.000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1456124

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

724576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000270

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1819G>A (p.G607S) alteration is located in exon 10 (coding exon 10) of the TRIM33 gene. This alteration results from a G to A substitution at nucleotide position 1819, causing the glycine (G) at amino acid position 607 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.13

Sift

Benign

0.75

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.57

P;P

Vest4

0.34

MutPred

0.24

Gain of phosphorylation at G607 (P = 0.0185);Gain of phosphorylation at G607 (P = 0.0185);

MVP

0.26

MPC

0.60

ClinPred

0.060

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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