Variant 5-177992589-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006261.5(PROP1):c.*120C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 679,534 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 2 hom., cov: 29)

Exomes 𝑓: 0.00074 ( 7 hom. )

Consequence

PROP1
NM_006261.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0510

Variant links:

Genes affected

PROP1 (HGNC:9455): (PROP paired-like homeobox 1) This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domain transcription factor 1, which is responsible for pituitary development and hormone expression. Mutations in this gene have been associated with combined pituitary hormone deficiency-2 as well as deficiencies in luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, and thyroid-stimulating hormone. [provided by RefSeq, Sep 2011]

PROP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 5-177992589-G-A is Benign according to our data. Variant chr5-177992589-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1810604.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (846/152152) while in subpopulation AFR AF= 0.0197 (816/41506). AF 95% confidence interval is 0.0185. There are 2 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROP1	NM_006261.5 linkuse as main transcript	c.*120C>T		3_prime_UTR_variant	3/3	ENST00000308304.2	NP_006252.4	O75360A0A0G2JQ02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROP1	ENST00000308304 linkuse as main transcript	c.*120C>T		3_prime_UTR_variant	3/3	1	NM_006261.5	ENSP00000311290.2		O75360

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

845

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.000741

AC:

391

AN:

527382

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

185

AN XY:

275000

show subpopulations

Gnomad4 AFR exome

AF:

0.0207

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.0000685

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0000619

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000326

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152152

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

391

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.00633

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.4

DANN

Benign

0.35

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over