chr10-133230671-C-T

Variant names:

• chr10-133230671-C-T
• rs1845786006
• NM_003577.3:c.383C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0640
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10076097).

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.383C>T	p.Ala128Val	missense	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.383C>T	p.Ala128Val	missense	Exon 1 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000523 AC: 7 AN: 1337896 Hom.: 0 Cov.: 35 AF XY: 0.00000905 AC XY: 6 AN XY: 663246

African (AFR) AF: 0.00 AC: 0 AN: 27948

American (AMR) AF: 0.00 AC: 0 AN: 28930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22960

East Asian (EAS) AF: 0.00 AC: 0 AN: 29960

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 73896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.00000566 AC: 6 AN: 1060402

Other (OTH) AF: 0.00 AC: 0 AN: 54874

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.064
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.086
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.036	D
Polyphen		0.95	P
Vest4		0.15
MutPred		0.19		Gain of helix (P = 0.0854)
MVP		0.072
MPC		1.6
ClinPred		0.35	T
GERP RS		1.9
PromoterAI		-0.025	Neutral
Varity_R		0.13
gMVP		0.018
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1845786006; hg19: chr10-135044175;