rs61751266

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_020366.4(RPGRIP1):​c.1107delA​(p.Glu370AsnfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000411 in 1,458,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. K369K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RPGRIP1
NM_020366.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:15O:1

Conservation

PhyloP100: 4.34

Publications

6 publications found
Variant links:
Genes affected
RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]
RPGRIP1 Gene-Disease associations (from GenCC):
  • cone-rod dystrophy 13
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
  • Leber congenital amaurosis 6
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • cone-rod dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Leber congenital amaurosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 16 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 14-21312457-GA-G is Pathogenic according to our data. Variant chr14-21312457-GA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 99809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020366.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPGRIP1
NM_020366.4
MANE Select
c.1107delAp.Glu370AsnfsTer5
frameshift
Exon 10 of 25NP_065099.3

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RPGRIP1
ENST00000400017.7
TSL:1 MANE Select
c.1107delAp.Glu370AsnfsTer5
frameshift
Exon 10 of 25ENSP00000382895.2Q96KN7-1
RPGRIP1
ENST00000557771.5
TSL:5
c.1026delAp.Glu343AsnfsTer5
frameshift
Exon 9 of 24ENSP00000451219.1G3V3F7
RPGRIP1
ENST00000556336.5
TSL:5
c.1026delAp.Glu343AsnfsTer5
frameshift
Exon 9 of 21ENSP00000450445.1G3V236

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
246030
AF XY:
0.00
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:
0.00000411
AC:
6
AN:
1458418
Hom.:
0
Cov.:
28
AF XY:
0.00000551
AC XY:
4
AN XY:
725500
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33366
American (AMR)
AF:
0.00
AC:
0
AN:
44328
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26064
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39612
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85652
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53364
Middle Eastern (MID)
AF:
0.000695
AC:
4
AN:
5756
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1110042
Other (OTH)
AF:
0.00
AC:
0
AN:
60234
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31

ClinVar

ClinVar submissions
Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
10
-
-
Leber congenital amaurosis 6 (10)
2
-
-
Cone-rod dystrophy 13 (2)
1
-
-
Leber congenital amaurosis (1)
1
-
-
Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 (1)
1
-
-
not provided (2)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.3
Mutation Taster
=0/200
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs61751266; hg19: chr14-21780616; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.