Genetic Variant NM_003577.3:c.217G>A (chr10-133230505-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003577.3(UTF1):c.217G>A(p.Gly73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,444,072 control chromosomes in the GnomAD database, including 12,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.099 ( 983 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11402 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17

Publications

15 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017513335).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTF1	NM_003577.3 link	c.217G>A	p.Gly73Arg	missense_variant	Exon 1 of 2	ENST00000304477.3	NP_003568.2	Q5T230

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTF1	ENST00000304477.3 link	c.217G>A	p.Gly73Arg	missense_variant	Exon 1 of 2	1	NM_003577.3	ENSP00000305906.2		Q5T230

Frequencies

GnomAD3 genomes

AF:

0.0990

AC:

14969

AN:

151258

Hom.:

982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.157

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.151

AC:

10919

AN:

72356

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.0949

Gnomad EAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.128

AC:

165385

AN:

1292706

Hom.:

11402

Cov.:

AF XY:

0.130

AC XY:

83071

AN XY:

637704

show subpopulations

African (AFR)

AF:

0.0231

AC:

604

AN:

26120

American (AMR)

AF:

0.186

AC:

4545

AN:

24482

Ashkenazi Jewish (ASJ)

AF:

0.0963

AC:

2141

AN:

22230

East Asian (EAS)

AF:

0.122

AC:

3256

AN:

26710

South Asian (SAS)

AF:

0.200

AC:

14147

AN:

70704

European-Finnish (FIN)

AF:

0.134

AC:

4317

AN:

32164

Middle Eastern (MID)

AF:

0.119

AC:

450

AN:

3772

European-Non Finnish (NFE)

AF:

0.125

AC:

129509

AN:

1033652

Other (OTH)

AF:

0.121

AC:

6416

AN:

52872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

8909

17818

26726

35635

44544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4906

9812

14718

19624

24530

<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:

0.0989

AC:

14964

AN:

151366

Hom.:

983

Cov.:

AF XY:

0.101

AC XY:

7504

AN XY:

73970

show subpopulations

African (AFR)

AF:

0.0258

AC:

1071

AN:

41472

American (AMR)

AF:

0.139

AC:

2111

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.0878

AC:

304

AN:

3464

East Asian (EAS)

AF:

0.114

AC:

581

AN:

5116

South Asian (SAS)

AF:

0.191

AC:

921

AN:

4826

European-Finnish (FIN)

AF:

0.136

AC:

1392

AN:

10250

Middle Eastern (MID)

AF:

0.155

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.121

AC:

8206

AN:

67746

Other (OTH)

AF:

0.105

AC:

220

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

695

1391

2086

2782

3477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.111

Hom.:

418

Bravo

AF:

0.0933

TwinsUK

AF:

0.119

AC:

442

ALSPAC

AF:

0.117

AC:

450

ExAC

AF:

0.0958

AC:

2091

Asia WGS

AF:

0.139

AC:

465

AN:

3350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.2

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.048

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.023

Polyphen

0.53

Vest4

0.043

MutPred

0.16

Gain of MoRF binding (P = 0.0054);

MPC

1.8

ClinPred

0.016

GERP RS

2.0

PromoterAI

-0.0049

Neutral

(source)

Varity_R

0.23

gMVP

0.024

Mutation Taster

=95/5

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over