chr11-111357618-T-G

Position:

• chr11-111357618-T-G

Variant summary

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

The NM_006235.3(POU2AF1):​c.283A>C​(p.Thr95Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU2AF1 NM_006235.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.353

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF1 (HGNC:):

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=0.2108199).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2AF1	NM_006235.3	c.283A>C	p.Thr95Pro	missense_variant	4/5	ENST00000393067.8	NP_006226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000393067.8	c.283A>C	p.Thr95Pro	missense_variant	4/5	1	NM_006235.3	ENSP00000376786.3
POU2AF1	ENST00000531398.1	c.289A>C	p.Thr97Pro	missense_variant	5/5	4		ENSP00000433527.1
POU2AF1	ENST00000525584.1	n.402A>C		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 28, 2021

The c.283A>C (p.T95P) alteration is located in exon 4 (coding exon 4) of the POU2AF1 gene. This alteration results from a A to C substitution at nucleotide position 283, causing the threonine (T) at amino acid position 95 to be replaced by a proline (P). 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	0.080
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0010	B;.
Vest4		0.26
MutPred		0.54		Loss of phosphorylation at T95 (P = 0.021);.;
MVP		0.26
MPC		0.63
ClinPred		0.46	T
GERP RS		1.6
Varity_R		0.27
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs1591190546; hg19: chr11-111228343;