rs376560556

Variant names:

• chr11-111308120-A-C
• NM_001271458.2:c.439A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-111308120-A-C
• chr11-111308120-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271458.2(POU2AF3):​c.439A>C​(p.Ser147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.2e-7 (0 hom.)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32547766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.439A>C	p.Ser147Arg	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.439A>C	p.Ser147Arg	missense_variant	Exon 5 of 5	1	NM_001271458.2	ENSP00000484135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394288 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 687212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000204

Gnomad4 NFE exome AF: 0.00

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;.;.;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.79	T;T;T;T;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	.;.;.;L;L;L
PROVEAN	Pathogenic	-4.8	.;.;D;.;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	.;.;D;.;D;D
Sift4G	Uncertain	0.0090	D;.;D;D;D;D
Polyphen		0.99	.;.;.;D;D;D
Vest4		0.53
MutPred		0.21		.;.;Loss of phosphorylation at S50 (P = 0.017);Loss of phosphorylation at S50 (P = 0.017);Loss of phosphorylation at S50 (P = 0.017);Loss of phosphorylation at S50 (P = 0.017);
MVP		0.13
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-111178845;