rs6537825

Variant names:

• chr1-114405659-A-G
• rs6537825
• NM_015906.4:c.2519T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-114405659-A-G
• chr1-114405659-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015906.4(TRIM33):​c.2519T>C​(p.Ile840Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 1,614,150 control chromosomes in the GnomAD database, including 684,209 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. I840S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.92 (64802 hom., cov: 32)
  • Exomes 𝑓: 0.92 (619407 hom.)
• Consequence: TRIM33 NM_015906.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 65 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.423833E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

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.2519T>C	p.Ile840Thr	missense	Exon 15 of 20	NP_056990.3
	TRIM33	NM_033020.3		c.2519T>C	p.Ile840Thr	missense	Exon 15 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.2519T>C	p.Ile840Thr	missense	Exon 15 of 20	ENSP00000351250.2	Q9UPN9-1
	TRIM33	ENST00000369543.6	TSL:1	c.2519T>C	p.Ile840Thr	missense	Exon 15 of 19	ENSP00000358556.2	Q9UPN9-2
	TRIM33	ENST00000925754.1		c.2612T>C	p.Ile871Thr	missense	Exon 16 of 20	ENSP00000595813.1

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139880 AN: 152152 Hom.: 64745 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.885

GnomAD2 exomes AF: 0.885 AC: 222458 AN: 251428 AF XY: 0.890

Gnomad AFR exome AF: 0.971

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.890

Gnomad EAS exome AF: 0.596

Gnomad FIN exome AF: 0.965

Gnomad NFE exome AF: 0.927

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.919 AC: 1342815 AN: 1461880 Hom.: 619407 Cov.: 65 AF XY: 0.919 AC XY: 668340 AN XY: 727242

African (AFR) AF: 0.972 AC: 32534 AN: 33480

American (AMR) AF: 0.780 AC: 34863 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 23255 AN: 26136

East Asian (EAS) AF: 0.644 AC: 25557 AN: 39698

South Asian (SAS) AF: 0.919 AC: 79263 AN: 86256

European-Finnish (FIN) AF: 0.964 AC: 51506 AN: 53420

Middle Eastern (MID) AF: 0.852 AC: 4913 AN: 5768

European-Non Finnish (NFE) AF: 0.932 AC: 1036681 AN: 1112004

Other (OTH) AF: 0.898 AC: 54243 AN: 60394

GnomAD4 genome AF: 0.919 AC: 139994 AN: 152270 Hom.: 64802 Cov.: 32 AF XY: 0.917 AC XY: 68252 AN XY: 74450

African (AFR) AF: 0.970 AC: 40315 AN: 41570

American (AMR) AF: 0.838 AC: 12800 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3081 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3087 AN: 5162

South Asian (SAS) AF: 0.916 AC: 4426 AN: 4830

European-Finnish (FIN) AF: 0.966 AC: 10248 AN: 10610

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63102 AN: 68032

Other (OTH) AF: 0.884 AC: 1868 AN: 2112

Alfa AF: 0.916 Hom.: 313103

Bravo AF: 0.907

TwinsUK AF: 0.926 AC: 3432

ALSPAC AF: 0.936 AC: 3607

ESP6500AA AF: 0.971 AC: 4280

ESP6500EA AF: 0.927 AC: 7976

ExAC AF: 0.892 AC: 108296

Asia WGS AF: 0.794 AC: 2761 AN: 3478

EpiCase AF: 0.916

EpiControl AF: 0.916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.30
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.062	T
MetaRNN	Benign	5.4e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.0	N
PhyloP100		3.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.66
ClinPred		0.0029	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6537825; hg19: chr1-114948281; COSMIC: COSV61821233;