rs1048635

Positions:

• chr1-117112236-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025188.4(TRIM45):​c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,406,222 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (215 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1765 hom.)
• Consequence: TRIM45 NM_025188.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

Genes affected

TRIM45 (HGNC:19018): (tripartite motif containing 45) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within bone development. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM45	NM_025188.4	c.*69C>T		3_prime_UTR_variant	6/6	ENST00000256649.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM45	ENST00000256649.9	c.*69C>T		3_prime_UTR_variant	6/6	1	NM_025188.4	P1
TRIM45	ENST00000369464.7	c.*69C>T		3_prime_UTR_variant	6/6	1
TRIM45	ENST00000369461.3	c.*69C>T		3_prime_UTR_variant	7/7	5
TRIM45	ENST00000497970.5	c.*69C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7421 AN: 152158 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.0544

GnomAD4 exome AF: 0.0524 AC: 65718 AN: 1253946 Hom.: 1765 Cov.: 24 AF XY: 0.0529 AC XY: 32324 AN XY: 611184

Gnomad4 AFR exome AF: 0.0338

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0437

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.0711

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0533

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.0488 AC: 7435 AN: 152276 Hom.: 215 Cov.: 32 AF XY: 0.0481 AC XY: 3579 AN XY: 74470

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.0733

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0553

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0542 Hom.: 299

Bravo AF: 0.0500

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs1048635; hg19: chr1-117654858; COSMIC: COSV56713375; COSMIC: COSV56713375;