Variant 10-133231089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003577.3(UTF1):c.673G>A(p.Ala225Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 848,374 control chromosomes in the GnomAD database, including 19 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0070 ( 3 hom., cov: 22)

Exomes 𝑓: 0.0082 ( 16 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030716956).

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTF1	NM_003577.3 linkuse as main transcript	c.673G>A	p.Ala225Thr	missense_variant	2/2	ENST00000304477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTF1	ENST00000304477.3 linkuse as main transcript	c.673G>A	p.Ala225Thr	missense_variant	2/2	1	NM_003577.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

541

AN:

77102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.00773

Gnomad ASJ

AF:

0.00294

Gnomad EAS

AF:

0.000365

Gnomad SAS

AF:

0.00176

Gnomad FIN

AF:

0.00213

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00995

Gnomad OTH

AF:

0.00517

GnomAD3 exomes

AF:

0.00360

AC:

AN:

11400

Hom.:

AF XY:

0.00368

AC XY:

AN XY:

7060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000655

Gnomad FIN exome

AF:

0.00105

Gnomad NFE exome

AF:

0.00705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00821

AC:

6332

AN:

771258

Hom.:

Cov.:

AF XY:

0.00826

AC XY:

3068

AN XY:

371428

show subpopulations

Gnomad4 AFR exome

AF:

0.000605

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00263

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000619

Gnomad4 FIN exome

AF:

0.00130

Gnomad4 NFE exome

AF:

0.00936

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.00702

AC:

541

AN:

77116

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

233

AN XY:

37178

show subpopulations

Gnomad4 AFR

AF:

0.00240

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.00294

Gnomad4 EAS

AF:

0.000365

Gnomad4 SAS

AF:

0.00176

Gnomad4 FIN

AF:

0.00213

Gnomad4 NFE

AF:

0.00995

Gnomad4 OTH

AF:

0.00513

Alfa

AF:

0.00251

Hom.:

ExAC

AF:

0.000575

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.673G>A (p.A225T) alteration is located in exon 2 (coding exon 2) of the UTF1 gene. This alteration results from a G to A substitution at nucleotide position 673, causing the alanine (A) at amino acid position 225 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

Cadd

Benign

0.90

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0058

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.29

M_CAP

Benign

0.027

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.45

REVEL

Benign

0.019

Sift

Benign

0.38

Sift4G

Benign

0.64

Polyphen

0.27

Vest4

0.046

MVP

0.014

MPC

1.4

ClinPred

0.022

GERP RS

-0.74

Varity_R

0.029

gMVP

0.024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over