dbSNP rs1061118: POU5F1:p.Ser349Ser (chr6-31164637-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002701.6(POU5F1):c.1047C>T(p.Ser349Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,581,374 control chromosomes in the GnomAD database, including 353,998 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 0.69 ( 36738 hom., cov: 31)

Exomes 𝑓: 0.66 ( 317260 hom. )

Consequence

POU5F1
NM_002701.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

Variant links:

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]

POU5F1 links:

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]

TCF19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=0.008 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6 link	c.1047C>T	p.Ser349Ser	synonymous_variant	Exon 5 of 5	ENST00000259915.13	NP_002692.2	Q01860-1D2IYK3
POU5F1	NM_001173531.3 link	c.537C>T	p.Ser179Ser	synonymous_variant	Exon 5 of 5		NP_001167002.1	M1S623
POU5F1	NM_203289.6 link	c.537C>T	p.Ser179Ser	synonymous_variant	Exon 4 of 4		NP_976034.4	M1S623
POU5F1	NM_001285986.2 link	c.459C>T	p.Ser153Ser	synonymous_variant	Exon 3 of 3		NP_001272915.1	F2Z381

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13 link	c.1047C>T	p.Ser349Ser	synonymous_variant	Exon 5 of 5	1	NM_002701.6	ENSP00000259915.7		Q01860-1

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104888

AN:

151832

Hom.:

36709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.636

AC:

114474

AN:

180008

Hom.:

36722

AF XY:

0.633

AC XY:

61221

AN XY:

96642

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.664

AC:

949796

AN:

1429426

Hom.:

317260

Cov.:

AF XY:

0.661

AC XY:

468185

AN XY:

707962

show subpopulations

Gnomad4 AFR exome

AF:

0.796

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.718

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.673

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.691

AC:

104965

AN:

151948

Hom.:

36738

Cov.:

AF XY:

0.685

AC XY:

50837

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.792

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.568

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.662

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.677

Hom.:

6357

Bravo

AF:

0.705

Asia WGS

AF:

0.664

AC:

2308

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.7

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over