10-133230298-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_003577.3(UTF1):c.10C>A(p.Arg4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,069,632 control chromosomes in the GnomAD database, including 384,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45012 hom., cov: 31)
  • Exomes 𝑓: 0.86 (339558 hom.)
• Consequence: UTF1 NM_003577.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.569

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 10-133230298-C-A is Benign according to our data. Variant chr10-133230298-C-A is described in ClinVar as [Benign]. Clinvar id is 2787236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.569 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTF1	NM_003577.3	c.10C>A	p.Arg4=	synonymous_variant	1/2	ENST00000304477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTF1	ENST00000304477.3	c.10C>A	p.Arg4=	synonymous_variant	1/2	1	NM_003577.3	P1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 114359 AN: 148960 Hom.: 44975 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.843

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.858 AC: 789540 AN: 920564 Hom.: 339558 Cov.: 41 AF XY: 0.859 AC XY: 371435 AN XY: 432550

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.839

Gnomad4 EAS exome AF: 0.731

Gnomad4 SAS exome AF: 0.781

Gnomad4 FIN exome AF: 0.856

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.829

GnomAD4 genome AF: 0.768 AC: 114447 AN: 149068 Hom.: 45012 Cov.: 31 AF XY: 0.769 AC XY: 55901 AN XY: 72738

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.788

Alfa AF: 0.796 Hom.: 7084

Bravo AF: 0.757

Asia WGS AF: 0.707 AC: 2188 AN: 3092

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	9.9
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs7092433; hg19: chr10-135043802; COSMIC: COSV58678831; COSMIC: COSV58678831;