17-44207100-ATTTTT-ATTT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

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. 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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4	c.*140_*141delAA		3_prime_UTR_variant	Exon 21 of 21	ENST00000436088.6	NP_055048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088	c.*140_*141delAA		3_prime_UTR_variant	Exon 21 of 21	2	NM_014233.4	ENSP00000390669.1

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

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00733

Gnomad4 EAS exome AF: 0.00511

Gnomad4 SAS exome AF: 0.00738

Gnomad4 FIN exome AF: 0.00422

Gnomad4 NFE exome AF: 0.00864

Gnomad4 OTH exome AF: 0.00710

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

Gnomad4 AFR AF: 0.000564

Gnomad4 AMR AF: 0.0000730

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000623

Gnomad4 NFE AF: 0.000112

Gnomad4 OTH AF: 0.000546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs374363130; hg19: chr17-42284468;