10-133230709-C-G

Variant names:

• chr10-133230709-C-G
• rs762112204
• NM_003577.3:c.421C>G

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.421C>G​(p.Arg141Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000302 in 1,323,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R141W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: UTF1 NM_003577.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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=0.24615541).

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.421C>G	p.Arg141Gly	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.421C>G	p.Arg141Gly	missense	Exon 1 of 2	ENSP00000305906.2	Q5T230

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000302 AC: 4 AN: 1323924 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 655766

African (AFR) AF: 0.00 AC: 0 AN: 27732

American (AMR) AF: 0.00 AC: 0 AN: 27526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22560

East Asian (EAS) AF: 0.00 AC: 0 AN: 29498

South Asian (SAS) AF: 0.00 AC: 0 AN: 72430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4574

European-Non Finnish (NFE) AF: 0.00000380 AC: 4 AN: 1051746

Other (OTH) AF: 0.00 AC: 0 AN: 54244

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.020
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.038	D
Sift4G	Benign	0.40	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.27		Loss of MoRF binding (P = 0.0401)
MVP		0.067
MPC		1.5
ClinPred		0.48	T
GERP RS		2.0
PromoterAI		-0.15	Neutral
Varity_R		0.11
gMVP		0.084
Mutation Taster		=92/8	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: rs762112204; hg19: chr10-135044213;