3-87259754-TAA-TA

Variant names:

• chr3-87259754-TA-T
• rs368061882
• NM_000306.4:c.*139delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000306.4(POU1F1):​c.*139delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 653,992 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00068 (3 hom.)
• Consequence: POU1F1 NM_000306.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000244 (37/151652) while in subpopulation SAS AF = 0.00685 (33/4818). AF 95% confidence interval is 0.00501. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR,SD gene

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.*139delT		3_prime_UTR	Exon 6 of 6	NP_000297.1	P28069-1
	POU1F1	NM_001122757.3		c.*139delT		3_prime_UTR	Exon 6 of 6	NP_001116229.1	P28069-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU1F1	ENST00000350375.7	TSL:1 MANE Select	c.*139delT		3_prime_UTR	Exon 6 of 6	ENSP00000263781.2	P28069-1
	POU1F1	ENST00000344265.8	TSL:5	c.*139delT		3_prime_UTR	Exon 6 of 6	ENSP00000342931.3	P28069-2
	POU1F1	ENST00000561167.5	TSL:5	c.*140delT		downstream_gene	N/A	ENSP00000454072.1	H0YNM5

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151536 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000681 AC: 342 AN: 502340 Hom.: 3 Cov.: 7 AF XY: 0.000967 AC XY: 258 AN XY: 266926

African (AFR) AF: 0.000225 AC: 3 AN: 13320

American (AMR) AF: 0.000161 AC: 3 AN: 18576

Ashkenazi Jewish (ASJ) AF: 0.0000674 AC: 1 AN: 14842

East Asian (EAS) AF: 0.00 AC: 0 AN: 30434

South Asian (SAS) AF: 0.00635 AC: 297 AN: 46796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2112

European-Non Finnish (NFE) AF: 0.0000663 AC: 21 AN: 316754

Other (OTH) AF: 0.000615 AC: 17 AN: 27634

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151652 Hom.: 0 Cov.: 31 AF XY: 0.000337 AC XY: 25 AN XY: 74100

African (AFR) AF: 0.0000484 AC: 2 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00685 AC: 33 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67886

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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: rs368061882; hg19: chr3-87308904;