Variant chr6-75922121-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_001563.4(IMPG1):c.2362G>T(p.Glu788Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IMPG1
NM_001563.4 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.661

Variant links:

Genes affected

IMPG1 (HGNC:6055): (interphotoreceptor matrix proteoglycan 1) This gene encodes a protein that is a major component of the retinal interphotoreceptor matrix. The encoded protein is a proteoglycan that is thought to play a role in maintaining viability of photoreceptor cells and in adhesion of the neural retina to the retinal pigment epithelium. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

IMPG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0134 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IMPG1	NM_001563.4 linkuse as main transcript	c.2362G>T	p.Glu788Ter	stop_gained	17/17	ENST00000369950.8
IMPG1	NM_001282368.2 linkuse as main transcript	c.2128G>T	p.Glu710Ter	stop_gained	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IMPG1	ENST00000369950.8 linkuse as main transcript	c.2362G>T	p.Glu788Ter	stop_gained	17/17	1	NM_001563.4	P2	Q17R60-1
IMPG1	ENST00000611179.4 linkuse as main transcript	c.2128G>T	p.Glu710Ter	stop_gained	16/16	5		A2
IMPG1	ENST00000369952.3 linkuse as main transcript	c.445G>T	p.Glu149Ter	stop_gained	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1230202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

619738

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Vitelliform macular dystrophy 4

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Goettingen

Jan 11, 2023

The variant c.2362G>T (p.(Glu788*)) in exon 17 of the IMPG1 gene is not found in the gnomAD database and it changes the protein sequence at position 788 and interrupts the reading frame prematurely by generating a STOP codon. As the variant most likely removes <10% of the protein, ACMG criterion PVS1_mod is applied. This variant was identified in a patient with a clinical diagnosis of Stargardt disease, who also carried two pathogenic ABCA4 mutations and one disease associated variant in ABCA4 (c.2588G>C (p.(Gly863Ala)), c.5882G>A (p.(Gly1961Glu)) and c.5603A>T (p.(Asn1868Ile)), respectively). ACMG criteria used for classification: PVS1_mod, PM2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.55

BayesDel_noAF

Pathogenic

0.55

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.43

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.76

MutationTaster

Benign

1.0

D;D

Vest4

0.10

GERP RS

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 45

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over