11-111308204-C-T

Variant names:

• chr11-111308204-C-T
• rs1391190802
• NM_001271458.2:c.523C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271458.2(POU2AF3):​c.523C>T​(p.Pro175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16824132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.523C>T	p.Pro175Ser	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.523C>T	p.Pro175Ser	missense_variant	Exon 5 of 5	1	NM_001271458.2	ENSP00000484135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;.;T;T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.66	T;T;T;T;.;.
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;.;.;L;L;L
PROVEAN	Pathogenic	-7.7	.;.;D;.;D;D
REVEL	Benign	0.12
Sift	Benign	0.075	.;.;T;.;T;T
Sift4G	Benign	0.21	T;.;D;D;D;D
Polyphen		0.28	.;.;.;B;B;B
Vest4		0.21
MutPred		0.15		.;.;Loss of catalytic residue at P78 (P = 0.0094);Loss of catalytic residue at P78 (P = 0.0094);Loss of catalytic residue at P78 (P = 0.0094);Loss of catalytic residue at P78 (P = 0.0094);
MVP		0.030
ClinPred		0.18	T
GERP RS		-0.35
Varity_R		0.082
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs1391190802; hg19: chr11-111178929; COSMIC: COSV67695252; COSMIC: COSV67695252;