10-133231018-C-A

Variant names:

• chr10-133231018-C-A
• rs1207261451
• NM_003577.3:c.602C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003577.3(UTF1):​c.602C>A​(p.Thr201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,183,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T201M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: UTF1 NM_003577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058152318).

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.602C>A	p.Thr201Lys	missense	Exon 2 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.602C>A	p.Thr201Lys	missense	Exon 2 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1183610 Hom.: 0 Cov.: 34 AF XY: 0.00000173 AC XY: 1 AN XY: 576808

African (AFR) AF: 0.00 AC: 0 AN: 23452

American (AMR) AF: 0.00 AC: 0 AN: 11216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16612

East Asian (EAS) AF: 0.00 AC: 0 AN: 26384

South Asian (SAS) AF: 0.00 AC: 0 AN: 48474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3202

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 979184

Other (OTH) AF: 0.0000210 AC: 1 AN: 47540

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.087
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.011
Sift	Benign	0.50	T
Sift4G	Benign	0.57	T
Polyphen		0.087	B
Vest4		0.18
MutPred		0.29		Gain of methylation at T201 (P = 0.0053)
MVP		0.014
MPC		1.1
ClinPred		0.037	T
GERP RS		-3.2
Varity_R		0.055
gMVP		0.036
Mutation Taster		=96/4	polymorphism

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: rs1207261451; hg19: chr10-135044522;