17-44207100-ATTTTT-ATTTTTT

Variant names:

• chr17-44207100-A-AT
• rs374363130
• NM_014233.4:c.*141dupA

Variant summary

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

The NM_014233.4(UBTF):​c.*141dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 798,076 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 0.00096 (0 hom., cov: 29)
  • Exomes 𝑓: 0.021 (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 131 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.*141dupA		3_prime_UTR	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.*141dupA		3_prime_UTR	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.*141dupA		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.*141dupA		3_prime_UTR	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.*141dupA		3_prime_UTR	Exon 20 of 20	ENSP00000345297.5	P17480-2
	UBTF	ENST00000905798.1		c.*141dupA		splice_region	Exon 21 of 21	ENSP00000575857.1

Frequencies

GnomAD3 genomes AF: 0.000957 AC: 131 AN: 136912 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00215

Gnomad EAS AF: 0.00294

Gnomad SAS AF: 0.00162

Gnomad FIN AF: 0.00211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0210 AC: 13905 AN: 661170 Hom.: 0 Cov.: 0 AF XY: 0.0206 AC XY: 6989 AN XY: 338550

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

African (AFR) AF: 0.0184 AC: 299 AN: 16236

American (AMR) AF: 0.0114 AC: 219 AN: 19144

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 231 AN: 14918

East Asian (EAS) AF: 0.0112 AC: 351 AN: 31312

South Asian (SAS) AF: 0.0187 AC: 909 AN: 48574

European-Finnish (FIN) AF: 0.0103 AC: 300 AN: 29146

Middle Eastern (MID) AF: 0.0144 AC: 34 AN: 2358

European-Non Finnish (NFE) AF: 0.0235 AC: 10966 AN: 466864

Other (OTH) AF: 0.0183 AC: 596 AN: 32618

⚠️ 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: 0.000957 AC: 131 AN: 136906 Hom.: 0 Cov.: 29 AF XY: 0.000890 AC XY: 59 AN XY: 66268

African (AFR) AF: 0.000644 AC: 24 AN: 37270

American (AMR) AF: 0.00109 AC: 15 AN: 13720

Ashkenazi Jewish (ASJ) AF: 0.00215 AC: 7 AN: 3260

East Asian (EAS) AF: 0.00295 AC: 14 AN: 4746

South Asian (SAS) AF: 0.00163 AC: 7 AN: 4306

European-Finnish (FIN) AF: 0.00211 AC: 17 AN: 8062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000751 AC: 47 AN: 62574

Other (OTH) AF: 0.00 AC: 0 AN: 1840

Alfa AF: 0.000314 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.014
Mutation Taster		=100/0	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;