rs777305639

Variant names:

• chr17-44207332-CTCG-C
• rs777305639
• NM_014233.4:c.2202_2204delCGA

Your query was ambiguous. Multiple possible variants found:

• chr17-44207332-CTCG-C
• chr17-44207332-CTCG-CTCGTCG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_014233.4(UBTF):​c.2202_2204delCGA​(p.Asp734del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000362 in 1,612,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00034 (0 hom.)
• Consequence: UBTF NM_014233.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.02
• Publications: 0 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_014233.4
• BP6: Variant 17-44207332-CTCG-C is Benign according to our data. Variant chr17-44207332-CTCG-C is described in ClinVar as Benign. ClinVar VariationId is 2243923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 84 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.2202_2204delCGA	p.Asp734del	disruptive_inframe_deletion	Exon 21 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.2091_2093delCGA	p.Asp697del	disruptive_inframe_deletion	Exon 20 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.2091_2093delCGA	p.Asp697del	disruptive_inframe_deletion	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.2202_2204delCGA	p.Asp734del	disruptive_inframe_deletion	Exon 21 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000529383.5	TSL:1	c.2202_2204delCGA	p.Asp734del	disruptive_inframe_deletion	Exon 20 of 20	ENSP00000435708.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.2091_2093delCGA	p.Asp697del	disruptive_inframe_deletion	Exon 20 of 20	ENSP00000345297.5	P17480-2

Frequencies

GnomAD3 genomes AF: 0.000553 AC: 84 AN: 152020 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000701

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000478 AC: 118 AN: 246648 AF XY: 0.000420

Gnomad AFR exome AF: 0.000819

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.00322

Gnomad EAS exome AF: 0.000275

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000288

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000342 AC: 500 AN: 1460400 Hom.: 0 AF XY: 0.000339 AC XY: 246 AN XY: 726358

African (AFR) AF: 0.00105 AC: 35 AN: 33440

American (AMR) AF: 0.000360 AC: 16 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00376 AC: 98 AN: 26054

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39642

South Asian (SAS) AF: 0.000605 AC: 52 AN: 85940

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53370

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.000223 AC: 248 AN: 1111392

Other (OTH) AF: 0.000447 AC: 27 AN: 60350

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152138 Hom.: 0 Cov.: 30 AF XY: 0.000578 AC XY: 43 AN XY: 74384

African (AFR) AF: 0.000699 AC: 29 AN: 41490

American (AMR) AF: 0.000654 AC: 10 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67982

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000618 Hom.: 0

Bravo AF: 0.000642

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0
Mutation Taster		=72/28	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: rs777305639; hg19: chr17-42284700; COSMIC: COSV57188416; COSMIC: COSV57188416;