rs540046911

Variant names:

• chr11-111308430-A-C
• NM_001271458.2:c.749A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-111308430-A-C
• chr11-111308430-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001271458.2(POU2AF3):​c.749A>C​(p.Tyr250Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000718 in 1,392,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 4.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.749A>C	p.Tyr250Ser	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.749A>C	p.Tyr250Ser	missense_variant	Exon 5 of 5	1	NM_001271458.2	ENSP00000484135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392046 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685778

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.71	T;T;T;.;.
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.7	.;.;L;L;L
PROVEAN	Pathogenic	-8.7	.;.;.;D;D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	.;.;.;D;D
Sift4G	Uncertain	0.013	D;.;D;D;D
Polyphen		1.0	.;.;D;D;D
Vest4		0.81
MutPred		0.35		.;.;Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);
MVP		0.18
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.15

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: chr11-111179155;