11-111357618-T-C

Variant names:

• chr11-111357618-T-C
• rs1591190546
• NM_006235.3:c.283A>G

Variant summary

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

The NM_006235.3(POU2AF1):​c.283A>G​(p.Thr95Ala) 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. 15/22 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. T95N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU2AF1 NM_006235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• agammaglobulinemia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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=0.10501805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006235.3. 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
	POU2AF1	NM_006235.3	MANE Select	c.283A>G	p.Thr95Ala	missense	Exon 4 of 5	NP_006226.2	Q16633

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF1	ENST00000393067.8	TSL:1 MANE Select	c.283A>G	p.Thr95Ala	missense	Exon 4 of 5	ENSP00000376786.3	Q16633
	POU2AF1	ENST00000531398.1	TSL:4	c.289A>G	p.Thr97Ala	missense	Exon 5 of 5	ENSP00000433527.1	E9PKH4
	POU2AF1	ENST00000525584.1	TSL:3	n.402A>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.35
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.058
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.39		Loss of glycosylation at T95 (P = 0.0134)
MVP		0.15
MPC		0.26
ClinPred		0.058	T
GERP RS		1.6
Varity_R		0.037
gMVP		0.35
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1591190546; hg19: chr11-111228343;