Variant rs773894295 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

The NM_178857.6(RP1L1):c.3956_3957insAAGAAGAGGG(p.Val1320ArgfsTer10) 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 0.0026 ( 5 hom., cov: 19)

Exomes 𝑓: 0.0015 ( 59 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]

RP1L1 links:

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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 21 pathogenic variants in the truncated region.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RP1L1	NM_178857.6 linkuse as main transcript	c.3956_3957insAAGAAGAGGG	p.Val1320ArgfsTer10	frameshift_variant	4/4	ENST00000382483.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RP1L1	ENST00000382483.4 linkuse as main transcript	c.3956_3957insAAGAAGAGGG	p.Val1320ArgfsTer10	frameshift_variant	4/4	1	NM_178857.6	P1	Q8IWN7-1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

396

AN:

149764

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00226

Gnomad ASJ

AF:

0.0117

Gnomad EAS

AF:

0.000791

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.000578

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00195

Gnomad OTH

AF:

0.00242

GnomAD3 exomes

AF:

0.000501

AC:

122

AN:

243342

Hom.:

AF XY:

0.000568

AC XY:

AN XY:

132050

show subpopulations

Gnomad AFR exome

AF:

0.00214

Gnomad AMR exome

AF:

0.000412

Gnomad ASJ exome

AF:

0.000823

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.0000945

Gnomad NFE exome

AF:

0.000557

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00146

AC:

1985

AN:

1363938

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1049

AN XY:

677300

show subpopulations

Gnomad4 AFR exome

AF:

0.00361

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.00820

Gnomad4 EAS exome

AF:

0.000674

Gnomad4 SAS exome

AF:

0.000980

Gnomad4 FIN exome

AF:

0.00301

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00264

AC:

396

AN:

149878

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

201

AN XY:

73242

show subpopulations

Gnomad4 AFR

AF:

0.00408

Gnomad4 AMR

AF:

0.00225

Gnomad4 ASJ

AF:

0.0117

Gnomad4 EAS

AF:

0.000595

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.000578

Gnomad4 NFE

AF:

0.00195

Gnomad4 OTH

AF:

0.00239

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over