rs13409

chr6-31164363-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_002701.6(POU5F1):c.*238C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,151,312 control chromosomes in the GnomAD database, including 110,166 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (14696 hom., cov: 32)
  • Exomes 𝑓: 0.43 (95470 hom.)
• Consequence: POU5F1 NM_002701.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.*238C>T		3_prime_UTR_variant	5/5	ENST00000259915.13
POU5F1	NM_001173531.3	c.*238C>T		3_prime_UTR_variant	5/5
POU5F1	NM_001285986.2	c.*238C>T		3_prime_UTR_variant	3/3
POU5F1	NM_203289.6	c.*238C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.*238C>T		3_prime_UTR_variant	5/5	1	NM_002701.6	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66531 AN: 151722 Hom.: 14690 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.434 AC: 433392 AN: 999472 Hom.: 95470 Cov.: 13 AF XY: 0.431 AC XY: 213177 AN XY: 494714

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.438 AC: 66564 AN: 151840 Hom.: 14696 Cov.: 32 AF XY: 0.433 AC XY: 32130 AN XY: 74212

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.413

Alfa AF: 0.429 Hom.: 4716

Bravo AF: 0.448

Asia WGS AF: 0.398 AC: 1381 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
Cadd	Benign	16
Dann	Benign	0.93

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: rs13409; hg19: chr6-31132140; COSMIC: COSV52563452; COSMIC: COSV52563452;