Genetic Variant UTF1:p.Pro133Ser (chr10-133230685-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003577.3(UTF1):c.397C>T(p.Pro133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,336,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0333986).

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.397C>T	p.Pro133Ser	missense	Exon 1 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.397C>T	p.Pro133Ser	missense	Exon 1 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

124516

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000299

AC:

AN:

1336644

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

662876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27948

American (AMR)

AF:

0.00

AC:

AN:

29082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22864

East Asian (EAS)

AF:

0.00

AC:

AN:

29964

South Asian (SAS)

AF:

0.0000271

AC:

AN:

73696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4732

European-Non Finnish (NFE)

AF:

0.00000189

AC:

AN:

1059372

Other (OTH)

AF:

0.00

AC:

AN:

54808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

0.077

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.45

M_CAP

Benign

0.035

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.20

PhyloP100

0.071

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.060

MutPred

0.21

Loss of catalytic residue at P132 (P = 0.0168)

MVP

0.014

MPC

0.93

ClinPred

0.098

GERP RS

-1.5

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.054

gMVP

0.015

Mutation Taster

=95/5

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