1-114427278-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015906.4(TRIM33):​c.1319G>A​(p.Arg440His) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,574,710 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: TRIM33 NM_015906.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• Publications: 7 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20927459).

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>A	p.Arg440His	missense	Exon 8 of 20	NP_056990.3
	TRIM33	NM_033020.3		c.1319G>A	p.Arg440His	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>A	p.Arg440His	missense	Exon 8 of 20	ENSP00000351250.2	Q9UPN9-1
	TRIM33	ENST00000369543.6	TSL:1	c.1319G>A	p.Arg440His	missense	Exon 8 of 19	ENSP00000358556.2	Q9UPN9-2
	TRIM33	ENST00000925754.1		c.1412G>A	p.Arg471His	missense	Exon 9 of 20	ENSP00000595813.1

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000126 AC: 3 AN: 238290 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000565

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000913 AC: 13 AN: 1423568 Hom.: 0 Cov.: 25 AF XY: 0.00000990 AC XY: 7 AN XY: 706812

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

American (AMR) AF: 0.0000239 AC: 1 AN: 41834

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25282

East Asian (EAS) AF: 0.0000513 AC: 2 AN: 39012

South Asian (SAS) AF: 0.0000248 AC: 2 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: 0.00000644 AC: 7 AN: 1086864

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

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151142 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73680

African (AFR) AF: 0.0000243 AC: 1 AN: 41174

American (AMR) AF: 0.00 AC: 0 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67772

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.36	N
PhyloP100		4.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.32
Sift	Benign	0.18	T
Sift4G	Benign	0.29	T
Polyphen		0.062	B
Vest4		0.33
MutPred		0.46		Loss of MoRF binding (P = 0.0096)
MVP		0.41
MPC		1.5
ClinPred		0.68	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.85
Mutation Taster		=90/10	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; COSMIC: COSV61822813;