chr1-114405659-A-T

Position:

• chr1-114405659-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015906.4(TRIM33):​c.2519T>A​(p.Ile840Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I840T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM33 NM_015906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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 (HGNC:):

ACMG classification

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=0.09375027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM33	NM_015906.4	c.2519T>A	p.Ile840Asn	missense_variant	15/20	ENST00000358465.7	NP_056990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM33	ENST00000358465.7	c.2519T>A	p.Ile840Asn	missense_variant	15/20	1	NM_015906.4	ENSP00000351250.2
TRIM33	ENST00000369543.6	c.2519T>A	p.Ile840Asn	missense_variant	15/19	1		ENSP00000358556.2
TRIM33	ENST00000448034.5	c.1799T>A	p.Ile600Asn	missense_variant	13/18	5		ENSP00000402333.1
TRIM33	ENST00000476908.1	n.128T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.88	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.35		Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);
MVP		0.18
MPC		0.93
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.13
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

Other links and lift over

dbSNP: rs6537825; hg19: chr1-114948281;