rs369739158

Variant names:

• chr3-87259746-CTTT-C
• rs369739158
• NM_000306.4:c.*145_*147delAAA

Your query was ambiguous. Multiple possible variants found:

• chr3-87259746-CTTT-C
• chr3-87259746-CTTT-CT
• chr3-87259746-CTTT-CTT
• chr3-87259746-CTTT-CTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000306.4(POU1F1):​c.*145_*147delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000198 in 504,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: POU1F1 NM_000306.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*145_*147delAAA		3_prime_UTR	Exon 6 of 6	NP_000297.1	P28069-1
	POU1F1	NM_001122757.3		c.*145_*147delAAA		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.*145_*147delAAA		3_prime_UTR	Exon 6 of 6	ENSP00000263781.2	P28069-1
	POU1F1	ENST00000344265.8	TSL:5	c.*145_*147delAAA		3_prime_UTR	Exon 6 of 6	ENSP00000342931.3	P28069-2
	POU1F1	ENST00000561167.5	TSL:5	c.*146_*148delAAA		downstream_gene	N/A	ENSP00000454072.1	H0YNM5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000198 AC: 1 AN: 504158 Hom.: 0 AF XY: 0.00000373 AC XY: 1 AN XY: 268394

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13286

American (AMR) AF: 0.00 AC: 0 AN: 18380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14608

East Asian (EAS) AF: 0.00 AC: 0 AN: 30240

South Asian (SAS) AF: 0.00 AC: 0 AN: 46262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2116

European-Non Finnish (NFE) AF: 0.00000312 AC: 1 AN: 320294

Other (OTH) AF: 0.00 AC: 0 AN: 27626

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

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: rs369739158; hg19: chr3-87308896;