chr17-44207100-AT-A

Position:

• chr17-44207100-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014233.4(UBTF):​c.*141del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 136,616 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (45 hom., cov: 29)
  • Exomes 𝑓: 0.39 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBTF NM_014233.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 17-44207100-AT-A is Benign according to our data. Variant chr17-44207100-AT-A is described in ClinVar as [Benign]. Clinvar id is 1258422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0255 (3483/136616) while in subpopulation AFR AF= 0.0489 (1822/37246). AF 95% confidence interval is 0.047. There are 45 homozygotes in gnomad4. There are 1752 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3483 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBTF	NM_014233.4	c.*141del		3_prime_UTR_variant	21/21	ENST00000436088.6	NP_055048.1
ATXN7L3-AS1	NR_184071.1	n.91+8185del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6	c.*141del		3_prime_UTR_variant	21/21	2	NM_014233.4	ENSP00000390669	P1
ATXN7L3-AS1	ENST00000586560.1	n.53+8181del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3474 AN: 136622 Hom.: 45 Cov.: 29

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.00504

Gnomad SAS AF: 0.00347

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0276

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0225

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.389 AC: 230016 AN: 590750 Hom.: 6 Cov.: 0 AF XY: 0.393 AC XY: 118450 AN XY: 301566

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.0255 AC: 3483 AN: 136616 Hom.: 45 Cov.: 29 AF XY: 0.0265 AC XY: 1752 AN XY: 66088

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0261

Gnomad4 EAS AF: 0.00506

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0229

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

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;