chr10-133230697-G-C

Variant names:

• chr10-133230697-G-C
• rs1845786629
• NM_003577.3:c.409G>C

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.409G>C​(p.Asp137His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000337 in 1,484,094 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: UTF1 NM_003577.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70
• 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=0.2195814).

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.409G>C	p.Asp137His	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.409G>C	p.Asp137His	missense	Exon 1 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151490 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000225 AC: 3 AN: 1332496 Hom.: 0 Cov.: 35 AF XY: 0.00000151 AC XY: 1 AN XY: 660662

African (AFR) AF: 0.00 AC: 0 AN: 27856

American (AMR) AF: 0.00 AC: 0 AN: 28562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22736

East Asian (EAS) AF: 0.00 AC: 0 AN: 29842

South Asian (SAS) AF: 0.00 AC: 0 AN: 73266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056898

Other (OTH) AF: 0.0000549 AC: 3 AN: 54612

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151598 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74096

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67822

Other (OTH) AF: 0.00 AC: 0 AN: 2102

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Pathogenic	0.97
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.017
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.14		Gain of MoRF binding (P = 0.0632)
MVP		0.081
MPC		2.2
ClinPred		0.71	D
GERP RS		3.0
PromoterAI		0.039	Neutral
Varity_R		0.17
gMVP		0.11
Mutation Taster		=91/9	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: rs1845786629; hg19: chr10-135044201;