11-111308208-C-T

Variant names:

• chr11-111308208-C-T
• rs201045815
• NM_001271458.2:c.527C>T

Variant summary

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

The NM_001271458.2(POU2AF3):​c.527C>T​(p.Pro176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,532 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: 0.0000036 (0 hom.)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• 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: 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=0.13766411).

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.527C>T	p.Pro176Leu	missense	Exon 5 of 5	NP_001258387.1	A8K830-5
	POU2AF3	NM_001136105.3		c.236C>T	p.Pro79Leu	missense	Exon 5 of 5	NP_001129577.1	A8K830-1
	POU2AF3	NM_001271457.2		c.236C>T	p.Pro79Leu	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.527C>T	p.Pro176Leu	missense	Exon 5 of 5	ENSP00000484135.1	A8K830-5
	POU2AF3	ENST00000638573.1	TSL:1	c.632C>T	p.Pro211Leu	missense	Exon 6 of 6	ENSP00000492570.1	A8K830-4
	POU2AF3	ENST00000398035.6	TSL:1	c.236C>T	p.Pro79Leu	missense	Exon 5 of 5	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000636 AC: 1 AN: 157260 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000164

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399532 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690264

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 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: 49330

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5700

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078998

Other (OTH) AF: 0.00 AC: 0 AN: 58042

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000225 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.34
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.11
Sift	Benign	0.056	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.76	P
Vest4		0.092
MutPred		0.21		Gain of catalytic residue at P79 (P = 0.0116)
MVP		0.22
ClinPred		0.31	T
GERP RS		5.0
Varity_R		0.082
gMVP		0.074
Mutation Taster		=98/2	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: rs201045815; hg19: chr11-111178933;