Variant 4-15994028-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_006017.3(PROM1):c.1726C>T(p.Gln576*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

PROM1
NM_006017.3 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:4

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

PROM1 (HGNC:9454): (prominin 1) This gene encodes a pentaspan transmembrane glycoprotein. The protein localizes to membrane protrusions and is often expressed on adult stem cells, where it is thought to function in maintaining stem cell properties by suppressing differentiation. Mutations in this gene have been shown to result in retinitis pigmentosa and Stargardt disease. Expression of this gene is also associated with several types of cancer. This gene is expressed from at least five alternative promoters that are expressed in a tissue-dependent manner. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

PROM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 4-15994028-G-A is Pathogenic according to our data. Variant chr4-15994028-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 5609.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-15994028-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROM1	NM_006017.3 linkuse as main transcript	c.1726C>T	p.Gln576*	stop_gained	16/28	ENST00000447510.7	NP_006008.1	O43490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROM1	ENST00000447510.7 linkuse as main transcript	c.1726C>T	p.Gln576*	stop_gained	16/28	1	NM_006017.3	ENSP00000415481.2		O43490-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249070

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Pathogenic:2

Pathogenic, criteria provided, single submitter	research	Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	May 27, 2024	- -
Pathogenic, no assertion criteria provided	clinical testing	Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	Jan 30, 2015	- -

Retinitis pigmentosa 41

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2007

- -

Retinitis pigmentosa

Pathogenic:1

Pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.27

Eigen_PC

Benign

-0.0056

FATHMM_MKL

Benign

0.65

Vest4

0.86

GERP RS

3.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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