chr1-114405659-A-G

Position:

• chr1-114405659-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.423833E-7).
• BP6: Variant 1-114405659-A-G is Benign according to our data. Variant chr1-114405659-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM33	NM_015906.4	c.2519T>C	p.Ile840Thr	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>C	p.Ile840Thr	missense_variant	15/20	1	NM_015906.4	ENSP00000351250.2
TRIM33	ENST00000369543.6	c.2519T>C	p.Ile840Thr	missense_variant	15/19	1		ENSP00000358556.2
TRIM33	ENST00000448034.5	c.1799T>C	p.Ile600Thr	missense_variant	13/18	5		ENSP00000402333.1
TRIM33	ENST00000476908.1	n.128T>C		non_coding_transcript_exon_variant	2/2	2

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

GnomAD3 exomes AF: 0.885 AC: 222458 AN: 251428 Hom.: 99797 AF XY: 0.890 AC XY: 120959 AN XY: 135900

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 SAS exome AF: 0.921

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

Gnomad4 AFR exome AF: 0.972

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 0.964

Gnomad4 NFE exome AF: 0.932

Gnomad4 OTH exome AF: 0.898

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

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.884

Alfa AF: 0.916 Hom.: 161338

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 v4.3

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;T
MetaRNN	Benign	5.4e-7	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.0	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	2.3	N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6537825; hg19: chr1-114948281; COSMIC: COSV61821233;