GeneBe

8-10610141-C-CCTCTCTTCTTGCA

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_178857.6(RP1L1):​c.3956_3957insTGCAAGAAGAGAG​(p.Val1320AlafsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 19)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RP1L1
NM_178857.6 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.28
Variant links:
Genes affected
RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

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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. There are 10 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RP1L1NM_178857.6 linkc.3956_3957insTGCAAGAAGAGAG p.Val1320AlafsTer11 frameshift_variant Exon 4 of 4 ENST00000382483.4 NP_849188.4 Q8IWN7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RP1L1ENST00000382483.4 linkc.3956_3957insTGCAAGAAGAGAG p.Val1320AlafsTer11 frameshift_variant Exon 4 of 4 1 NM_178857.6 ENSP00000371923.3 Q8IWN7-1

Frequencies

GnomAD3 genomes
AF:
0.00000667
AC:
1
AN:
149906
Hom.:
0
Cov.:
19
show subpopulations
Gnomad AFR
AF:
0.0000249
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000147
AC:
2
AN:
1365082
Hom.:
0
Cov.:
38
AF XY:
0.00000148
AC XY:
1
AN XY:
677910
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:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.47e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000667
AC:
1
AN:
149906
Hom.:
0
Cov.:
19
AF XY:
0.0000137
AC XY:
1
AN XY:
73190
show subpopulations
Gnomad4 AFR
AF:
0.0000249
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs773894295; hg19: chr8-10467651; API