rs755058963

Variant names:

• chr1-114427278-C-A
• rs755058963
• NM_015906.4:c.1319G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-114427278-C-A
• chr1-114427278-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015906.4(TRIM33):​c.1319G>T​(p.Arg440Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,423,570 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R440H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TRIM33 NM_015906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• developmental dysplasia of the hip

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015906.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM33	NM_015906.4	MANE Select	c.1319G>T	p.Arg440Leu	missense	Exon 8 of 20	NP_056990.3
	TRIM33	NM_033020.3		c.1319G>T	p.Arg440Leu	missense	Exon 8 of 19	NP_148980.2	Q9UPN9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM33	ENST00000358465.7	TSL:1 MANE Select	c.1319G>T	p.Arg440Leu	missense	Exon 8 of 20	ENSP00000351250.2	Q9UPN9-1
	TRIM33	ENST00000369543.6	TSL:1	c.1319G>T	p.Arg440Leu	missense	Exon 8 of 19	ENSP00000358556.2	Q9UPN9-2
	TRIM33	ENST00000925754.1		c.1412G>T	p.Arg471Leu	missense	Exon 9 of 20	ENSP00000595813.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423570 Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1 AN XY: 706812

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32544

American (AMR) AF: 0.00 AC: 0 AN: 41834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 39012

South Asian (SAS) AF: 0.00 AC: 0 AN: 80800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086866

Other (OTH) AF: 0.00 AC: 0 AN: 58794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.14	T
Polyphen		0.15	B
Vest4		0.76
MutPred		0.54		Loss of MoRF binding (P = 0.0078)
MVP		0.59
MPC		2.2
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.95
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs755058963; hg19: chr1-114969900;