10-133231110-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003577.3(UTF1):c.694T>A(p.Cys232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,057,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: UTF1 NM_003577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050976425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTF1	NM_003577.3	c.694T>A	p.Cys232Ser	missense_variant	2/2	ENST00000304477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTF1	ENST00000304477.3	c.694T>A	p.Cys232Ser	missense_variant	2/2	1	NM_003577.3	P1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1057698 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 506020

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.694T>A (p.C232S) alteration is located in exon 2 (coding exon 2) of the UTF1 gene. This alteration results from a T to A substitution at nucleotide position 694, causing the cysteine (C) at amino acid position 232 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	2.2
Dann	Benign	0.76
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.0040
Sift	Uncertain	0.021	D
Sift4G	Benign	0.89	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.23		Gain of glycosylation at C232 (P = 0.007);
MVP		0.014
MPC		1.3
ClinPred		0.051	T
GERP RS		-0.53
Varity_R		0.23
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-135044614;