rs755058963

Variant names:

• chr1-114427278-C-A
• 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. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM33	NM_015906.4	c.1319G>T	p.Arg440Leu	missense_variant	Exon 8 of 20	ENST00000358465.7	NP_056990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM33	ENST00000358465.7	c.1319G>T	p.Arg440Leu	missense_variant	Exon 8 of 20	1	NM_015906.4	ENSP00000351250.2
TRIM33	ENST00000369543.6	c.1319G>T	p.Arg440Leu	missense_variant	Exon 8 of 19	1		ENSP00000358556.2
TRIM33	ENST00000448034.5	c.527G>T	p.Arg176Leu	missense_variant	Exon 5 of 18	5		ENSP00000402333.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0090	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.15	B;P
Vest4		0.76
MutPred		0.54		Loss of MoRF binding (P = 0.0078);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-114969900;