6-31164363-G-A

Variant names:

• chr6-31164363-G-A
• rs13409
• NM_002701.6:c.*238C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002701.6. 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
	POU5F1	NM_002701.6	MANE Select	c.*238C>T		3_prime_UTR	Exon 5 of 5	NP_002692.2
	POU5F1	NM_001173531.3		c.*238C>T		3_prime_UTR	Exon 5 of 5	NP_001167002.1
	POU5F1	NM_203289.6		c.*238C>T		3_prime_UTR	Exon 4 of 4	NP_976034.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.*238C>T		3_prime_UTR	Exon 5 of 5	ENSP00000259915.7
	POU5F1	ENST00000606567.6	TSL:1	c.*238C>T		3_prime_UTR	Exon 5 of 5	ENSP00000475880.2
	POU5F1	ENST00000441888.7	TSL:1	c.*238C>T		3_prime_UTR	Exon 5 of 5	ENSP00000389359.2

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

African (AFR) AF: 0.479 AC: 10601 AN: 22130

American (AMR) AF: 0.446 AC: 8560 AN: 19208

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 6877 AN: 16922

East Asian (EAS) AF: 0.360 AC: 11853 AN: 32922

South Asian (SAS) AF: 0.384 AC: 21243 AN: 55382

European-Finnish (FIN) AF: 0.365 AC: 15700 AN: 43060

Middle Eastern (MID) AF: 0.403 AC: 1212 AN: 3006

European-Non Finnish (NFE) AF: 0.444 AC: 338738 AN: 763430

Other (OTH) AF: 0.429 AC: 18608 AN: 43412

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

African (AFR) AF: 0.479 AC: 19816 AN: 41382

American (AMR) AF: 0.453 AC: 6906 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1964 AN: 5154

South Asian (SAS) AF: 0.373 AC: 1796 AN: 4816

European-Finnish (FIN) AF: 0.361 AC: 3806 AN: 10544

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29499 AN: 67912

Other (OTH) AF: 0.413 AC: 868 AN: 2100

Alfa AF: 0.439 Hom.: 31676

Bravo AF: 0.448

Asia WGS AF: 0.398 AC: 1381 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism (auto)

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