11-120298386-G-A

Position:

• chr11-120298386-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014352.4(POU2F3):​c.254G>A​(p.Cys85Tyr) 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU2F3 NM_014352.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.777

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093141764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2F3	NM_014352.4	c.254G>A	p.Cys85Tyr	missense_variant	4/13	ENST00000543440.7	NP_055167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2F3	ENST00000543440.7	c.254G>A	p.Cys85Tyr	missense_variant	4/13	1	NM_014352.4	ENSP00000441687.2
POU2F3	ENST00000533620.5	n.254G>A		non_coding_transcript_exon_variant	4/14	1		ENSP00000435738.2
POU2F3	ENST00000260264.8	c.260G>A	p.Cys87Tyr	missense_variant	4/13	2		ENSP00000260264.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

The c.254G>A (p.C85Y) alteration is located in exon 4 (coding exon 4) of the POU2F3 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the cysteine (C) at amino acid position 85 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.0
DANN	Benign	0.64
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.34	T
REVEL	Benign	0.23
Sift4G	Benign	0.17	T;T
Polyphen		0.0030	.;B
Vest4		0.26
MutPred		0.19		.;Gain of phosphorylation at C85 (P = 0.009);
MVP		0.48
MPC		0.39
ClinPred		0.051	T
GERP RS		-0.56
Varity_R		0.20
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-120169095;