11-111308330-G-T

Variant names:

• chr11-111308330-G-T
• rs372744042
• NM_001271458.2:c.649G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001271458.2(POU2AF3):​c.649G>T​(p.Ala217Ser) 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. 15/20 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. A217T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04161036).

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.649G>T	p.Ala217Ser	missense	Exon 5 of 5	NP_001258387.1	A8K830-5
	POU2AF3	NM_001136105.3		c.358G>T	p.Ala120Ser	missense	Exon 5 of 5	NP_001129577.1	A8K830-1
	POU2AF3	NM_001271457.2		c.358G>T	p.Ala120Ser	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.649G>T	p.Ala217Ser	missense	Exon 5 of 5	ENSP00000484135.1	A8K830-5
	POU2AF3	ENST00000638573.1	TSL:1	c.754G>T	p.Ala252Ser	missense	Exon 6 of 6	ENSP00000492570.1	A8K830-4
	POU2AF3	ENST00000398035.6	TSL:1	c.358G>T	p.Ala120Ser	missense	Exon 5 of 5	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 156456 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.033
DANN	Benign	0.77
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
PhyloP100		-0.27
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.0070
Sift	Benign	0.83	T
Sift4G	Benign	0.85	T
Polyphen		0.0060	B
Vest4		0.043
MutPred		0.31		Gain of disorder (P = 0.0434)
MVP		0.014
ClinPred		0.041	T
GERP RS		-2.0
Varity_R		0.042
gMVP		0.040
Mutation Taster		=100/0	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: rs372744042; hg19: chr11-111179055;