11-111308207-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 13/18 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.526C>T	p.Pro176Ser	missense_variant	Exon 5 of 5	ENST00000610738.6	NP_001258387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6	c.526C>T	p.Pro176Ser	missense_variant	Exon 5 of 5	1	NM_001271458.2	ENSP00000484135.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000560

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.52	T;T;T;T;.;.
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.037	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.63	.;.;.;N;N;N
PROVEAN	Benign	-1.5	.;.;N;.;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.27	.;.;T;.;T;T
Sift4G	Benign	0.46	T;.;T;T;T;T
Polyphen		0.0060	.;.;.;B;B;B
Vest4		0.052
MutPred		0.11		.;.;Loss of catalytic residue at P78 (P = 0.016);Loss of catalytic residue at P78 (P = 0.016);Loss of catalytic residue at P78 (P = 0.016);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

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: chr11-111178932;