17-44207502-G-A

Variant names:

• chr17-44207502-G-A
• rs148770098
• NM_014233.4:c.2121C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014233.4(UBTF):​c.2121C>T​(p.Gly707Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,613,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: UBTF NM_014233.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.744

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008147627).
• BP6: Variant 17-44207502-G-A is Benign according to our data. Variant chr17-44207502-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 780067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.744 with no splicing effect.
• BS2: High AC in GnomAd4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4	c.2121C>T	p.Gly707Gly	synonymous_variant	Exon 20 of 21	ENST00000436088.6	NP_055048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6	c.2121C>T	p.Gly707Gly	synonymous_variant	Exon 20 of 21	2	NM_014233.4	ENSP00000390669.1

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 62 AN: 151830 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000644 AC: 162 AN: 251364 AF XY: 0.000618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000395 AC: 578 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.000388 AC XY: 282 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33480

Gnomad4 AMR exome AF: 0.0000224 AC: 1 AN: 44722

Gnomad4 ASJ exome AF: 0.0108 AC: 282 AN: 26130

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000255 AC: 22 AN: 86254

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53418

Gnomad4 NFE exome AF: 0.000186 AC: 207 AN: 1112006

Gnomad4 Remaining exome AF: 0.00106 AC: 64 AN: 60396

GnomAD4 genome AF: 0.000408 AC: 62 AN: 151948 Hom.: 1 Cov.: 31 AF XY: 0.000323 AC XY: 24 AN XY: 74274

Gnomad4 AFR AF: 0.0000242 AC: 0.0000241616 AN: 0.0000241616

Gnomad4 AMR AF: 0.0000655 AC: 0.0000654707 AN: 0.0000654707

Gnomad4 ASJ AF: 0.0112 AC: 0.0112392 AN: 0.0112392

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000309 AC: 0.000309014 AN: 0.000309014

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000610 Hom.: 0

Bravo AF: 0.000510

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000511 AC: 62

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	3.7
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.27	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.0081	T
MetaSVM	Uncertain	0.59	D
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.32
Sift	Benign	0.034	D
Sift4G	Uncertain	0.035	D
Vest4		0.20
MVP		0.53
ClinPred		0.025	T
GERP RS		-0.77
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs148770098; hg19: chr17-42284870; COSMIC: COSV100256069; COSMIC: COSV100256069;