chr6-75922159-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001563.4(IMPG1):c.2324G>A(p.Ser775Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,303,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S775S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

IMPG1
NM_001563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.492

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

IMPG1-related dominant retinopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
vitelliform macular dystrophy 4
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
IMPG1-related recessive retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AR, AD Classification: MODERATE Submitted by: Franklin by Genoox
adult-onset foveomacular vitelliform dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IMPG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020748526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001563.4. 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
	IMPG1	NM_001563.4	MANE Select	c.2324G>A	p.Ser775Asn	missense	Exon 17 of 17	NP_001554.2
	IMPG1	NM_001282368.2		c.2090G>A	p.Ser697Asn	missense	Exon 16 of 16	NP_001269297.1	A0A087WYL3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IMPG1	ENST00000369950.8	TSL:1 MANE Select	c.2324G>A	p.Ser775Asn	missense	Exon 17 of 17	ENSP00000358966.3	Q17R60-1
IMPG1	ENST00000611179.4	TSL:5	c.2090G>A	p.Ser697Asn	missense	Exon 16 of 16	ENSP00000481913.1	A0A087WYL3
IMPG1	ENST00000369952.3	TSL:3	c.407G>A	p.Ser136Asn	missense	Exon 4 of 4	ENSP00000358968.3	Q5JSC4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000567

AC:

AN:

193868

AF XY:

0.0000484

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1151754

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

582358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27544

American (AMR)

AF:

0.00

AC:

AN:

38476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23660

East Asian (EAS)

AF:

0.00

AC:

AN:

37114

South Asian (SAS)

AF:

0.000184

AC:

AN:

75902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50236

Middle Eastern (MID)

AF:

0.000200

AC:

AN:

4988

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

844326

Other (OTH)

AF:

0.0000404

AC:

AN:

49508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74294

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000585

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.62

M_CAP

Benign

0.0049

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-0.49

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.40

REVEL

Benign

0.025

Sift

Benign

0.041

Sift4G

Benign

0.35

Polyphen

0.035

Vest4

0.085

MutPred

0.21

Loss of sheet (P = 0.0817)

MVP

0.24

MPC

0.014

ClinPred

0.019

GERP RS

-3.4

Varity_R

0.062

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over