17-44207341-G-T

Variant names:

• chr17-44207341-G-T
• rs145436194
• NM_014233.4:c.2196C>A

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.2196C>A​(p.Asp732Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: UBTF NM_014233.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.85

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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06786701).
• BP6: Variant 17-44207341-G-T is Benign according to our data. Variant chr17-44207341-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3185891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4	c.2196C>A	p.Asp732Glu	missense_variant	Exon 21 of 21	ENST00000436088.6	NP_055048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6	c.2196C>A	p.Asp732Glu	missense_variant	Exon 21 of 21	2	NM_014233.4	ENSP00000390669.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151908 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.0000405 AC: 10 AN: 247034 Hom.: 0 AF XY: 0.0000375 AC XY: 5 AN XY: 133498

Gnomad AFR exome AF: 0.000503

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460430 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8 AN XY: 726426

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000135

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151908 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74186

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00144

Bravo AF: 0.000223

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Dec 09, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	0.036
DANN	Benign	0.82
DEOGEN2	Benign	0.081	.;T;.;T;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.59	.;.;.;.;.;T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.068	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.088	D
MutationAssessor	Benign	0.85	.;L;.;L;.;.;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	0.090	N;N;N;N;N;N;N
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Benign	0.94	T;T;T;T;T;T;T
Polyphen		0.0020	B;B;B;B;B;B;B
Vest4		0.13
MutPred		0.13		.;Loss of loop (P = 0.1242);.;Loss of loop (P = 0.1242);.;.;Loss of loop (P = 0.1242);
MVP		0.47
MPC		0.23
ClinPred		0.040	T
GERP RS		-11
Varity_R		0.23
gMVP		0.0048

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: rs145436194; hg19: chr17-42284709;