rs557128089

Variant names:

• chr11-120307509-C-A
• rs557128089
• NM_014352.4:c.800C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-120307509-C-A
• chr11-120307509-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014352.4(POU2F3):​c.800C>A​(p.Thr267Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POU2F3 NM_014352.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• Publications: 2 publications found

Genes affected

POU2F3 (HGNC:19864): (POU class 2 homeobox 3) This gene encodes a member of the POU domain family of transcription factors. POU domain transcription factors bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. The encoded protein is primarily expressed in the epidermis, and plays a critical role in keratinocyte proliferation and differentiation. The encoded protein is also a candidate tumor suppressor protein, and aberrant promoter methylation of this gene may play a role in cervical cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

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=0.22152331).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014352.4. 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
	POU2F3	NM_014352.4	MANE Select	c.800C>A	p.Thr267Lys	missense	Exon 9 of 13	NP_055167.2	Q9UKI9-1
	POU2F3	NM_001244682.2		c.806C>A	p.Thr269Lys	missense	Exon 9 of 13	NP_001231611.1	Q9UKI9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2F3	ENST00000543440.7	TSL:1 MANE Select	c.800C>A	p.Thr267Lys	missense	Exon 9 of 13	ENSP00000441687.2	Q9UKI9-1
	POU2F3	ENST00000533620.5	TSL:1	n.*466C>A		non_coding_transcript_exon	Exon 10 of 14	ENSP00000435738.2	E9PIN6
	POU2F3	ENST00000533620.5	TSL:1	n.*466C>A		3_prime_UTR	Exon 10 of 14	ENSP00000435738.2	E9PIN6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.33
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	-0.20	N
PhyloP100		2.0
PrimateAI	Benign	0.42	T
REVEL	Benign	0.28
Sift4G	Uncertain	0.0050	D
Polyphen		0.72	P
Vest4		0.33
MutPred		0.37		Gain of ubiquitination at T267 (P = 7e-04)
MVP		0.76
MPC		0.40
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.50
Mutation Taster		=89/11	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: rs557128089; hg19: chr11-120178218;