11-111306577-T-G

Variant names:

• chr11-111306577-T-G
• rs201037042
• NM_001271458.2:c.341T>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001271458.2(POU2AF3):​c.341T>G​(p.Phe114Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,551,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: POU2AF3 NM_001271458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.487

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044735163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2	c.341T>G	p.Phe114Cys	missense_variant	Exon 4 of 5	ENST00000610738.6	NP_001258387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6	c.341T>G	p.Phe114Cys	missense_variant	Exon 4 of 5	1	NM_001271458.2	ENSP00000484135.1

Frequencies

GnomAD3 genomes AF: 0.000835 AC: 127 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000739 AC: 116 AN: 156964 Hom.: 0 AF XY: 0.000722 AC XY: 60 AN XY: 83066

Gnomad AFR exome AF: 0.000375

Gnomad AMR exome AF: 0.000284

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000966

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.000454

GnomAD4 exome AF: 0.00150 AC: 2098 AN: 1399448 Hom.: 1 Cov.: 31 AF XY: 0.00151 AC XY: 1039 AN XY: 690230

Gnomad4 AFR exome AF: 0.000316

Gnomad4 AMR exome AF: 0.000280

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000947

Gnomad4 FIN exome AF: 0.0000811

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.000827

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74468

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00139 Hom.: 1

Bravo AF: 0.000903

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00156 AC: 6

ExAC AF: 0.000598 AC: 15

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50T>G (p.F17C) alteration is located in exon 4 (coding exon 1) of the COLCA2 gene. This alteration results from a T to G substitution at nucleotide position 50, causing the phenylalanine (F) at amino acid position 17 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;.;T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.58	T;T;T;T;.;.
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.045	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;.;.;L;L;L
PROVEAN	Pathogenic	-6.9	.;.;D;.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	.;.;D;.;D;D
Sift4G	Uncertain	0.0070	D;.;D;D;D;D
Polyphen		0.051	.;.;.;B;B;B
Vest4		0.25
MVP		0.13
ClinPred		0.043	T
GERP RS		4.7
Varity_R		0.25
gMVP		0.16

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: rs201037042; hg19: chr11-111177302; COSMIC: COSV67695775; COSMIC: COSV67695775;