Genetic Variant POU1F1:c.*138_*139dupTT (chr3-87259754-T-TAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000306.4(POU1F1):c.*138_*139dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 654,192 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

POU1F1
NM_000306.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

Genes affected

POU1F1 (HGNC:9210): (POU class 1 homeobox 1) This gene encodes a member of the POU family of transcription factors that regulate mammalian development. The protein regulates expression of several genes involved in pituitary development and hormone expression. Mutations in this genes result in combined pituitary hormone deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

POU1F1 Gene-Disease associations (from GenCC):

pituitary hormone deficiency, combined, 1
Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
combined pituitary hormone deficiencies, genetic form
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypothyroidism due to deficient transcription factors involved in pituitary development or function
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
isolated growth hormone deficiency type II
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

POU1F1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000306.4. 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
	POU1F1	NM_000306.4	MANE Select	c.138_139dupTT		3_prime_UTR	Exon 6 of 6	NP_000297.1	P28069-1
	POU1F1	NM_001122757.3		c.138_139dupTT		3_prime_UTR	Exon 6 of 6	NP_001116229.1	P28069-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POU1F1	ENST00000350375.7	TSL:1 MANE Select	c.138_139dupTT	3_prime_UTR	Exon 6 of 6	ENSP00000263781.2	P28069-1
POU1F1	ENST00000344265.8	TSL:5	c.138_139dupTT	3_prime_UTR	Exon 6 of 6	ENSP00000342931.3	P28069-2
POU1F1	ENST00000561167.5	TSL:5	c.139_140dupTT	downstream_gene	N/A	ENSP00000454072.1	H0YNM5

Frequencies

GnomAD3 genomes

AF:

0.0000726

AC:

AN:

151538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000396

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.0000438

AC:

AN:

502538

Hom.:

Cov.:

AF XY:

0.0000562

AC XY:

AN XY:

267034

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13326

American (AMR)

AF:

0.000377

AC:

AN:

18580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14842

East Asian (EAS)

AF:

0.0000328

AC:

AN:

30476

South Asian (SAS)

AF:

0.00

AC:

AN:

46816

European-Finnish (FIN)

AF:

0.0000314

AC:

AN:

31882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2112

European-Non Finnish (NFE)

AF:

0.0000347

AC:

AN:

316860

Other (OTH)

AF:

0.0000723

AC:

AN:

27644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.423

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151654

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41364

American (AMR)

AF:

0.000395

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67886

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined Pituitary Hormone Deficiency, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-87259754-TAA-TAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over