6-75923668-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001563.4(IMPG1):​c.2282G>A​(p.Ser761Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,582,566 control chromosomes in the GnomAD database, including 47,346 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. S761S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 3225 hom., cov: 32)
Exomes 𝑓: 0.24 ( 44121 hom. )

Consequence

IMPG1
NM_001563.4 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013806224).
BP6
Variant 6-75923668-C-T is Benign according to our data. Variant chr6-75923668-C-T is described in ClinVar as [Benign]. Clinvar id is 1164207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-75923668-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IMPG1NM_001563.4 linkuse as main transcriptc.2282G>A p.Ser761Asn missense_variant 16/17 ENST00000369950.8
IMPG1NM_001282368.2 linkuse as main transcriptc.2048G>A p.Ser683Asn missense_variant 15/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IMPG1ENST00000369950.8 linkuse as main transcriptc.2282G>A p.Ser761Asn missense_variant 16/171 NM_001563.4 P2Q17R60-1
IMPG1ENST00000611179.4 linkuse as main transcriptc.2048G>A p.Ser683Asn missense_variant 15/165 A2
IMPG1ENST00000369952.3 linkuse as main transcriptc.365G>A p.Ser122Asn missense_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.185
AC:
28037
AN:
151950
Hom.:
3222
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0614
Gnomad AMI
AF:
0.161
Gnomad AMR
AF:
0.206
Gnomad ASJ
AF:
0.176
Gnomad EAS
AF:
0.0494
Gnomad SAS
AF:
0.148
Gnomad FIN
AF:
0.176
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.269
Gnomad OTH
AF:
0.209
GnomAD3 exomes
AF:
0.191
AC:
46441
AN:
243518
Hom.:
5029
AF XY:
0.194
AC XY:
25518
AN XY:
131524
show subpopulations
Gnomad AFR exome
AF:
0.0551
Gnomad AMR exome
AF:
0.174
Gnomad ASJ exome
AF:
0.166
Gnomad EAS exome
AF:
0.0506
Gnomad SAS exome
AF:
0.151
Gnomad FIN exome
AF:
0.176
Gnomad NFE exome
AF:
0.253
Gnomad OTH exome
AF:
0.224
GnomAD4 exome
AF:
0.239
AC:
342209
AN:
1430498
Hom.:
44121
Cov.:
26
AF XY:
0.238
AC XY:
169443
AN XY:
712744
show subpopulations
Gnomad4 AFR exome
AF:
0.0552
Gnomad4 AMR exome
AF:
0.180
Gnomad4 ASJ exome
AF:
0.170
Gnomad4 EAS exome
AF:
0.0507
Gnomad4 SAS exome
AF:
0.155
Gnomad4 FIN exome
AF:
0.182
Gnomad4 NFE exome
AF:
0.266
Gnomad4 OTH exome
AF:
0.220
GnomAD4 genome
AF:
0.184
AC:
28045
AN:
152068
Hom.:
3225
Cov.:
32
AF XY:
0.180
AC XY:
13348
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0614
Gnomad4 AMR
AF:
0.206
Gnomad4 ASJ
AF:
0.176
Gnomad4 EAS
AF:
0.0499
Gnomad4 SAS
AF:
0.148
Gnomad4 FIN
AF:
0.176
Gnomad4 NFE
AF:
0.269
Gnomad4 OTH
AF:
0.208
Alfa
AF:
0.245
Hom.:
7303
Bravo
AF:
0.181
TwinsUK
AF:
0.274
AC:
1017
ALSPAC
AF:
0.276
AC:
1065
ESP6500AA
AF:
0.0606
AC:
267
ESP6500EA
AF:
0.261
AC:
2239
ExAC
AF:
0.191
AC:
23135
Asia WGS
AF:
0.0920
AC:
322
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Retinal dystrophy Benign:1
Benign, criteria provided, single submitterresearchDept Of Ophthalmology, Nagoya UniversityOct 01, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.6
DANN
Benign
0.51
DEOGEN2
Benign
0.00035
T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.60
T;T;T
MetaRNN
Benign
0.014
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.2
L;.;.
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.32
N;.;N
REVEL
Benign
0.0090
Sift
Benign
0.97
T;.;T
Sift4G
Benign
0.64
T;T;T
Polyphen
0.0040
B;.;.
Vest4
0.069
MPC
0.013
ClinPred
0.00072
T
GERP RS
0.067
Varity_R
0.032
gMVP
0.24

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.

Other links and lift over

dbSNP: rs3778005; hg19: chr6-76633385; API