NM_002701.6:c.1047C>T

Variant names:

• chr6-31164637-G-A
• rs1061118
• NM_002701.6:c.1047C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 8 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.1047C>T	p.Ser349Ser	synonymous	Exon 5 of 5	NP_002692.2
	POU5F1	NM_001173531.3		c.537C>T	p.Ser179Ser	synonymous	Exon 5 of 5	NP_001167002.1	M1S623
	POU5F1	NM_203289.6		c.537C>T	p.Ser179Ser	synonymous	Exon 4 of 4	NP_976034.4	M1S623

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.1047C>T	p.Ser349Ser	synonymous	Exon 5 of 5	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000606567.6	TSL:1	c.537C>T	p.Ser179Ser	synonymous	Exon 5 of 5	ENSP00000475880.2	M1S623
	POU5F1	ENST00000441888.7	TSL:1	c.459C>T	p.Ser153Ser	synonymous	Exon 5 of 5	ENSP00000389359.2	F2Z381

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104888 AN: 151832 Hom.: 36709 Cov.: 31

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

GnomAD2 exomes AF: 0.636 AC: 114474 AN: 180008 AF XY: 0.633

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 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.: 52 AF XY: 0.661 AC XY: 468185 AN XY: 707962

African (AFR) AF: 0.796 AC: 26142 AN: 32854

American (AMR) AF: 0.608 AC: 23953 AN: 39386

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 18280 AN: 25460

East Asian (EAS) AF: 0.598 AC: 23044 AN: 38524

South Asian (SAS) AF: 0.581 AC: 47829 AN: 82290

European-Finnish (FIN) AF: 0.576 AC: 29593 AN: 51400

Middle Eastern (MID) AF: 0.682 AC: 3220 AN: 4722

European-Non Finnish (NFE) AF: 0.673 AC: 737799 AN: 1095598

Other (OTH) AF: 0.675 AC: 39936 AN: 59192

GnomAD4 genome AF: 0.691 AC: 104965 AN: 151948 Hom.: 36738 Cov.: 31 AF XY: 0.685 AC XY: 50837 AN XY: 74256

African (AFR) AF: 0.792 AC: 32828 AN: 41450

American (AMR) AF: 0.679 AC: 10362 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3262 AN: 5146

South Asian (SAS) AF: 0.568 AC: 2738 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 5997 AN: 10542

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45012 AN: 67944

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.681 Hom.: 6603

Bravo AF: 0.705

Asia WGS AF: 0.664 AC: 2308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		0.0080
Mutation Taster		=99/1	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: rs1061118; hg19: chr6-31132414; COSMIC: COSV52564205; COSMIC: COSV52564205;