17-44207100-ATTTTT-ATTT

Variant names:

• chr17-44207100-ATT-A
• rs374363130
• NM_014233.4:c.*140_*141delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014233.4(UBTF):​c.*140_*141delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 786,330 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0082 (0 hom.)
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 1 publications found

Genes affected

UBTF (HGNC:12511): (upstream binding transcription factor) This gene encodes a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions. The encoded protein may also play important roles in chromatin remodeling and pre-rRNA processing, and its activity is regulated by both phosphorylation and acetylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3, 11 and X and the long arm of chromosome 11. [provided by RefSeq, Aug 2011]

ATXN7L3-AS1 (HGNC:55298): (ATXN7L3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014233.4. 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
	UBTF	NM_014233.4	MANE Select	c.*140_*141delAA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*140_*141delAA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*140_*141delAA		3_prime_UTR	Exon 20 of 20	NP_001070152.1	P17480-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTF	ENST00000436088.6	TSL:2 MANE Select	c.*140_*141delAA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*140_*141delAA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*140_*141delAA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 35 AN: 136852 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000730

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000623

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000112

Gnomad OTH AF: 0.000546

GnomAD4 exome AF: 0.00824 AC: 5354 AN: 649478 Hom.: 0 AF XY: 0.00799 AC XY: 2657 AN XY: 332648

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0129 AC: 206 AN: 15960

American (AMR) AF: 0.0106 AC: 198 AN: 18750

Ashkenazi Jewish (ASJ) AF: 0.00733 AC: 108 AN: 14740

East Asian (EAS) AF: 0.00511 AC: 157 AN: 30734

South Asian (SAS) AF: 0.00738 AC: 351 AN: 47580

European-Finnish (FIN) AF: 0.00422 AC: 121 AN: 28660

Middle Eastern (MID) AF: 0.00904 AC: 21 AN: 2324

European-Non Finnish (NFE) AF: 0.00864 AC: 3964 AN: 458626

Other (OTH) AF: 0.00710 AC: 228 AN: 32104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000256 AC: 35 AN: 136852 Hom.: 0 Cov.: 29 AF XY: 0.000332 AC XY: 22 AN XY: 66212

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000564 AC: 21 AN: 37216

American (AMR) AF: 0.0000730 AC: 1 AN: 13708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3260

East Asian (EAS) AF: 0.00 AC: 0 AN: 4764

South Asian (SAS) AF: 0.00 AC: 0 AN: 4330

European-Finnish (FIN) AF: 0.000623 AC: 5 AN: 8026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000112 AC: 7 AN: 62566

Other (OTH) AF: 0.000546 AC: 1 AN: 1830

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000156518), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.046
Mutation Taster		=99/1	polymorphism

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: rs374363130; hg19: chr17-42284468;