1-52531568-T-C

Variant names:

• chr1-52531568-T-C
• rs835036
• NM_001009881.3:c.-93-5195A>G

Variant summary

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

The NM_001009881.3(TUT4):​c.-93-5195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,038 control chromosomes in the GnomAD database, including 9,167 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 0.31 (9167 hom., cov: 31)
• Consequence: TUT4 NM_001009881.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 8 publications found

Genes affected

TUT4 (HGNC:28981): (terminal uridylyl transferase 4) Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; negative regulation of transposition, RNA-mediated; and stem cell population maintenance. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleolus. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

LOC105378723 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009881.3. 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
	TUT4	NM_001009881.3	MANE Select	c.-93-5195A>G		intron	N/A	NP_001009881.1	Q5TAX3-3
	TUT4	NM_015269.2		c.-93-5195A>G		intron	N/A	NP_056084.1	Q5TAX3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUT4	ENST00000257177.9	TSL:1 MANE Select	c.-93-5195A>G		intron	N/A	ENSP00000257177.4	Q5TAX3-3
	TUT4	ENST00000484723.6	TSL:1	c.-5-15514A>G		intron	N/A	ENSP00000435256.1	E9PKX1
	TUT4	ENST00000355809.4	TSL:1	c.-93-5195A>G		intron	N/A	ENSP00000348063.4	X6R5G7

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46643 AN: 151920 Hom.: 9160 Cov.: 31

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46661 AN: 152038 Hom.: 9167 Cov.: 31 AF XY: 0.319 AC XY: 23720 AN XY: 74288

African (AFR) AF: 0.0860 AC: 3570 AN: 41500

American (AMR) AF: 0.480 AC: 7330 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.724 AC: 3735 AN: 5158

South Asian (SAS) AF: 0.416 AC: 2004 AN: 4820

European-Finnish (FIN) AF: 0.438 AC: 4618 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23204 AN: 67938

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.316 Hom.: 4800

Bravo AF: 0.301

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.58
DANN	Benign	0.86
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs835036; hg19: chr1-52997240;