Genetic Variant NM_003577.3:c.383C>T (chr10-133230671-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003577.3(UTF1):c.383C>T(p.Ala128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000523 in 1,337,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

UTF1
NM_003577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0640

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10076097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTF1	NM_003577.3 link	c.383C>T	p.Ala128Val	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.383C>T	p.Ala128Val	missense_variant	Exon 1 of 2	1	NM_003577.3	ENSP00000305906.2		Q5T230

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000523

AC:

AN:

1337896

Hom.:

Cov.:

AF XY:

0.00000905

AC XY:

AN XY:

663246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000566

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.383C>T (p.A128V) alteration is located in exon 1 (coding exon 1) of the UTF1 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the alanine (A) at amino acid position 128 to be replaced by a valine (V). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.9

REVEL

Benign

0.086

Sift

Uncertain

0.017

Sift4G

Uncertain

0.036

Polyphen

0.95

Vest4

0.15

MutPred

0.19

Gain of helix (P = 0.0854);

MVP

0.072

MPC

1.6

ClinPred

0.35

GERP RS

1.9

Varity_R

0.13

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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