17-44207861-C-T

Position:

• chr17-44207861-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014233.4(UBTF):​c.1953+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,064 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0023 (6 hom.)
• Consequence: UBTF NM_014233.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00004584
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.182

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)

MIR6782 (HGNC:50270): (microRNA 6782) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-44207861-C-T is Benign according to our data. Variant chr17-44207861-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647823.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-44207861-C-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBTF	NM_014233.4	c.1953+3G>A		splice_donor_region_variant, intron_variant		ENST00000436088.6	NP_055048.1
ATXN7L3-AS1	NR_184071.1	n.91+8931C>T		intron_variant, non_coding_transcript_variant
MIR6782	NR_106840.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6	c.1953+3G>A		splice_donor_region_variant, intron_variant		2	NM_014233.4	ENSP00000390669	P1
ATXN7L3-AS1	ENST00000586560.1	n.54-8230C>T		intron_variant, non_coding_transcript_variant		3
MIR6782	ENST00000619539.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152090 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00163 AC: 409 AN: 250822 Hom.: 1 AF XY: 0.00160 AC XY: 217 AN XY: 135672

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000948

Gnomad FIN exome AF: 0.00374

Gnomad NFE exome AF: 0.00243

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00228 AC: 3340 AN: 1461856 Hom.: 6 Cov.: 33 AF XY: 0.00233 AC XY: 1692 AN XY: 727224

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000812

Gnomad4 FIN exome AF: 0.00335

Gnomad4 NFE exome AF: 0.00265

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152208 Hom.: 1 Cov.: 31 AF XY: 0.00128 AC XY: 95 AN XY: 74430

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00219

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00138

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00224

EpiControl AF: 0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

UBTF: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000046
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs201459469; hg19: chr17-42285229;