17-44207100-ATTTTT-ATT

Variant names:

• chr17-44207100-ATTT-A
• rs374363130
• NM_014233.4:c.*139_*141delAAA

Variant summary

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

The NM_014233.4(UBTF):​c.*139_*141delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 666,318 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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.*139_*141delAAA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*139_*141delAAA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*139_*141delAAA		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.*139_*141delAAA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*139_*141delAAA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*139_*141delAAA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 136928 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000222 AC: 148 AN: 666318 Hom.: 0 AF XY: 0.000229 AC XY: 78 AN XY: 341242

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

African (AFR) AF: 0.000245 AC: 4 AN: 16358

American (AMR) AF: 0.000155 AC: 3 AN: 19296

Ashkenazi Jewish (ASJ) AF: 0.0000664 AC: 1 AN: 15060

East Asian (EAS) AF: 0.0000633 AC: 2 AN: 31610

South Asian (SAS) AF: 0.0000408 AC: 2 AN: 49034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29482

Middle Eastern (MID) AF: 0.000420 AC: 1 AN: 2382

European-Non Finnish (NFE) AF: 0.000283 AC: 133 AN: 470146

Other (OTH) AF: 0.0000607 AC: 2 AN: 32950

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 136928 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 66260

African (AFR) AF: 0.00 AC: 0 AN: 37222

American (AMR) AF: 0.00 AC: 0 AN: 13720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3258

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8060

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62592

Other (OTH) AF: 0.00 AC: 0 AN: 1830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

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;