ENST00000638573.1:c.37A>T

Variant names:

• chr11-111299815-A-T
• rs10891246
• ENST00000638573.1:c.37A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000638573.1(POU2AF3):​c.37A>T​(p.Thr13Ser) 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. 8/9 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU2AF3 ENST00000638573.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 11 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]

COLCA1 (HGNC:33789): (colorectal cancer associated 1) This gene encodes a transmembrane protein that localizes to granular structures, including crystalloid eosinophilic granules and other granular organelles. This gene, along with an overlapping opposite strand gene, has been implicated as a susceptibility locus for colorectal cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107586235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638573.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	NM_001271458.2	MANE Select	c.8-712A>T		intron	N/A	NP_001258387.1
	POU2AF3	NM_001370484.1		c.-487A>T		5_prime_UTR	Exon 1 of 5	NP_001357413.1
	POU2AF3	NM_001136105.3		c.-285+91A>T		intron	N/A	NP_001129577.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2AF3	ENST00000638573.1	TSL:1	c.37A>T	p.Thr13Ser	missense	Exon 2 of 6	ENSP00000492570.1
	COLCA1	ENST00000355430.5	TSL:1	n.99T>A		non_coding_transcript_exon	Exon 1 of 2
	POU2AF3	ENST00000639470.1	TSL:1	n.37A>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000492182.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 798072 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 383078

African (AFR) AF: 0.00 AC: 0 AN: 17536

American (AMR) AF: 0.00 AC: 0 AN: 8112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12626

East Asian (EAS) AF: 0.00 AC: 0 AN: 25298

South Asian (SAS) AF: 0.00 AC: 0 AN: 14018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 662200

Other (OTH) AF: 0.00 AC: 0 AN: 34666

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.76
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.11	T
PhyloP100		0.017
GERP RS		-5.7
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs10891246; hg19: chr11-111170540;