11-111308207-C-T

Variant names:

• chr11-111308207-C-T
• rs1016414091
• NM_001271458.2:c.526C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271458.2(POU2AF3):​c.526C>T​(p.Pro176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. P176Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 0 publications found

Genes affected

POU2AF3 (HGNC:26978): (POU class 2 homeobox associating factor 3) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03698057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271458.2. 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
	POU2AF3	NM_001271458.2	MANE Select	c.526C>T	p.Pro176Ser	missense	Exon 5 of 5	NP_001258387.1	A8K830-5
	POU2AF3	NM_001136105.3		c.235C>T	p.Pro79Ser	missense	Exon 5 of 5	NP_001129577.1	A8K830-1
	POU2AF3	NM_001271457.2		c.235C>T	p.Pro79Ser	missense	Exon 5 of 5	NP_001258386.1	A8K830-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	ENST00000610738.6	TSL:1 MANE Select	c.526C>T	p.Pro176Ser	missense	Exon 5 of 5	ENSP00000484135.1	A8K830-5
	POU2AF3	ENST00000638573.1	TSL:1	c.631C>T	p.Pro211Ser	missense	Exon 6 of 6	ENSP00000492570.1	A8K830-4
	POU2AF3	ENST00000398035.6	TSL:1	c.235C>T	p.Pro79Ser	missense	Exon 5 of 5	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399530 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690262

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000560 AC: 2 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078998

Other (OTH) AF: 0.00 AC: 0 AN: 58044

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.039
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.63	N
PhyloP100		-0.84
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.32
Sift	Benign	0.27	T
Sift4G	Benign	0.46	T
Polyphen		0.0060	B
Vest4		0.052
MutPred		0.11		Loss of catalytic residue at P78 (P = 0.016)
MVP		0.040
ClinPred		0.24	T
GERP RS		-6.1
Varity_R		0.017
gMVP		0.047
Mutation Taster		=99/1	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: rs1016414091; hg19: chr11-111178932;