chr17-44207100-ATTTTT-A

Variant names:

• chr17-44207100-ATTTTT-A
• rs374363130
• NM_014233.4:c.*137_*141delAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014233.4(UBTF):​c.*137_*141delAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 667,002 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 0 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 2 ACMG points.

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

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.*137_*141delAAAAA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*137_*141delAAAAA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*137_*141delAAAAA		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.*137_*141delAAAAA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*137_*141delAAAAA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*137_*141delAAAAA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000150 AC: 1 AN: 667002 Hom.: 0 AF XY: 0.00000293 AC XY: 1 AN XY: 341610

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

African (AFR) AF: 0.00 AC: 0 AN: 16378

American (AMR) AF: 0.00 AC: 0 AN: 19330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15078

East Asian (EAS) AF: 0.00 AC: 0 AN: 31632

South Asian (SAS) AF: 0.00 AC: 0 AN: 49082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2382

European-Non Finnish (NFE) AF: 0.00000212 AC: 1 AN: 470646

Other (OTH) AF: 0.00 AC: 0 AN: 32966

⚠️ 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 Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374363130; hg19: chr17-42284468;