Genetic Variant UTF1:p.Pro189Ser (chr10-133230981-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003577.3(UTF1):c.565C>T(p.Pro189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,326,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.646

Publications

0 publications found

Variant links:

Genes affected

UTF1 (HGNC:12634): (undifferentiated embryonic cell transcription factor 1) The protein encoded by this gene is a leucine zipper-containing transcriptional coactivator that may link the upstream activator ATF2 with the basal transcription complex. The encoded protein is closely associated with chromatin and is required for the proper differentiation of embryonic carcinoma and embryonic stem cells. Found nearly exclusively in pluripotent cells, this protein can also serve as a transcriptional repressor. [provided by RefSeq, Nov 2015]

UTF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070587516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003577.3. 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
	UTF1	NM_003577.3	MANE Select	c.565C>T	p.Pro189Ser	missense	Exon 2 of 2	NP_003568.2	Q5T230

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTF1	ENST00000304477.3	TSL:1 MANE Select	c.565C>T	p.Pro189Ser	missense	Exon 2 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1174998

Hom.:

Cov.:

AF XY:

0.00000876

AC XY:

AN XY:

570902

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23236

American (AMR)

AF:

0.00

AC:

AN:

10468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16146

East Asian (EAS)

AF:

0.00

AC:

AN:

26212

South Asian (SAS)

AF:

0.00

AC:

AN:

46956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3186

European-Non Finnish (NFE)

AF:

0.0000133

AC:

AN:

974282

Other (OTH)

AF:

0.0000212

AC:

AN:

47202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151398

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67732

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.16

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.36

M_CAP

Benign

0.037

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.65

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.0080

Sift

Benign

0.52

Sift4G

Benign

0.082

Polyphen

0.0070

Vest4

0.063

MutPred

0.22

Gain of phosphorylation at P189 (P = 0.0104)

MVP

0.040

MPC

1.2

ClinPred

0.14

GERP RS

0.94

Varity_R

0.052

gMVP

0.039

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over