Genetic Variant UTF1:p.Arg38Gln (chr10-133230401-G-A) – 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.113G>A(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,313,484 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 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.35

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=0.053361773).

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.113G>A	p.Arg38Gln	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.113G>A	p.Arg38Gln	missense	Exon 1 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1163638

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

567340

show subpopulations

African (AFR)

AF:

0.0000435

AC:

AN:

22970

American (AMR)

AF:

0.00

AC:

AN:

13866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16772

East Asian (EAS)

AF:

0.00

AC:

AN:

23872

South Asian (SAS)

AF:

0.00

AC:

AN:

50462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3106

European-Non Finnish (NFE)

AF:

0.0000552

AC:

AN:

959902

Other (OTH)

AF:

0.00

AC:

AN:

45650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00000667

AC:

AN:

149846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73104

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41100

American (AMR)

AF:

0.00

AC:

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9782

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67234

Other (OTH)

AF:

0.00

AC:

AN:

2068

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

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.48

M_CAP

Benign

0.012

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-1.3

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.36

REVEL

Benign

0.017

Sift

Benign

0.39

Sift4G

Benign

0.49

Polyphen

0.11

Vest4

0.077

MutPred

0.14

Loss of methylation at R38 (P = 0.0301)

MVP

0.030

MPC

1.1

ClinPred

0.065

GERP RS

-3.0

PromoterAI

-0.037

Neutral

(source)

Varity_R

0.025

gMVP

0.023

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over