NM_003577.3:c.10C>A

Variant names:

• chr10-133230298-C-A
• rs7092433
• NM_003577.3:c.10C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_003577.3(UTF1):​c.10C>A​(p.Arg4Arg) 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003577.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTF1	NM_003577.3	MANE Select	c.10C>A	p.Arg4Arg	synonymous	Exon 1 of 2	NP_003568.2	Q5T230

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTF1	ENST00000304477.3	TSL:1 MANE Select	c.10C>A	p.Arg4Arg	synonymous	Exon 1 of 2	ENSP00000305906.2	Q5T230

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

African (AFR) AF: 0.571 AC: 10054 AN: 17616

American (AMR) AF: 0.815 AC: 2968 AN: 3642

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 6422 AN: 7652

East Asian (EAS) AF: 0.731 AC: 5941 AN: 8126

South Asian (SAS) AF: 0.781 AC: 14180 AN: 18150

European-Finnish (FIN) AF: 0.856 AC: 8213 AN: 9594

Middle Eastern (MID) AF: 0.832 AC: 1705 AN: 2050

European-Non Finnish (NFE) AF: 0.868 AC: 713154 AN: 821284

Other (OTH) AF: 0.829 AC: 26903 AN: 32450

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

African (AFR) AF: 0.587 AC: 24117 AN: 41068

American (AMR) AF: 0.807 AC: 12136 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2822 AN: 3426

East Asian (EAS) AF: 0.693 AC: 3515 AN: 5072

South Asian (SAS) AF: 0.775 AC: 3738 AN: 4822

European-Finnish (FIN) AF: 0.829 AC: 7916 AN: 9548

Middle Eastern (MID) AF: 0.838 AC: 243 AN: 290

European-Non Finnish (NFE) AF: 0.860 AC: 57467 AN: 66822

Other (OTH) AF: 0.788 AC: 1636 AN: 2076

Alfa AF: 0.796 Hom.: 7084

Bravo AF: 0.757

Asia WGS AF: 0.707 AC: 2188 AN: 3092

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.9
DANN	Benign	0.80
PhyloP100		-0.57
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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