11-111354541-G-T

Variant names:

• chr11-111354541-G-T
• rs142246564
• NM_006235.3:c.491C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006235.3(POU2AF1):​c.491C>A​(p.Pro164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.2e-7 (0 hom.)
• Consequence: POU2AF1 NM_006235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [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=0.0559749).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF1	NM_006235.3	c.491C>A	p.Pro164Gln	missense_variant	Exon 5 of 5	ENST00000393067.8	NP_006226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000393067.8	c.491C>A	p.Pro164Gln	missense_variant	Exon 5 of 5	1	NM_006235.3	ENSP00000376786.3
POU2AF1	ENST00000525584.1	n.610C>A		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690170

Gnomad4 AFR exome AF: 0.0000329

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.1
DANN	Benign	0.25
DEOGEN2	Benign	0.094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.63	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.094
MutPred		0.34		Loss of glycosylation at P164 (P = 0.0551);
MVP		0.043
MPC		0.25
ClinPred		0.070	T
GERP RS		-0.63
Varity_R		0.042
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs142246564; hg19: chr11-111225266; COSMIC: COSV101260622; COSMIC: COSV101260622;