17-44207100-ATTTTT-ATTTTTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014233.4(UBTF):​c.*140_*141dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 803,468 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: 𝑓 0.000037 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

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_*141dupAA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*140_*141dupAA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*140_*141dupAA		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_*141dupAA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*140_*141dupAA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*140_*141dupAA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes AF: 0.0000365 AC: 5 AN: 136930 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000107

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: 0.0000160

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000270 AC: 180 AN: 666538 Hom.: 0 Cov.: 0 AF XY: 0.000272 AC XY: 93 AN XY: 341376

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

African (AFR) AF: 0.000794 AC: 13 AN: 16368

American (AMR) AF: 0.000207 AC: 4 AN: 19330

Ashkenazi Jewish (ASJ) AF: 0.000199 AC: 3 AN: 15068

East Asian (EAS) AF: 0.000126 AC: 4 AN: 31630

South Asian (SAS) AF: 0.000245 AC: 12 AN: 49068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29506

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

European-Non Finnish (NFE) AF: 0.000293 AC: 138 AN: 470242

Other (OTH) AF: 0.000182 AC: 6 AN: 32944

⚠️ 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: 0.0000365 AC: 5 AN: 136930 Hom.: 0 Cov.: 29 AF XY: 0.0000302 AC XY: 2 AN XY: 66256

African (AFR) AF: 0.000107 AC: 4 AN: 37222

American (AMR) AF: 0.00 AC: 0 AN: 13716

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: 0.00 AC: 0 AN: 8062

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

European-Non Finnish (NFE) AF: 0.0000160 AC: 1 AN: 62594

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.014

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;