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GeneBe

rs1554609956

chr8-86626026-AT-AAC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_019098.5(CNGB3):c.1534delinsGT(p.Ile512ValfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CNGB3
NM_019098.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.314
Variant links:
Genes affected
CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-86626027-T-AC is Pathogenic according to our data. Variant chr8-86626027-T-AC is described in ClinVar as [Pathogenic]. Clinvar id is 427664.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNGB3NM_019098.5 linkuse as main transcriptc.1534delinsGT p.Ile512ValfsTer2 frameshift_variant 13/18 ENST00000320005.6
CNGB3XM_011517138.3 linkuse as main transcriptc.1120delinsGT p.Ile374ValfsTer2 frameshift_variant 11/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNGB3ENST00000320005.6 linkuse as main transcriptc.1534delinsGT p.Ile512ValfsTer2 frameshift_variant 13/181 NM_019098.5 P1Q9NQW8-1
CNGB3ENST00000681546.1 linkuse as main transcriptn.1354delinsGT non_coding_transcript_exon_variant 8/13
CNGB3ENST00000681746.1 linkuse as main transcriptc.1534delinsGT p.Ile512ValfsTer2 frameshift_variant, NMD_transcript_variant 13/19

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Achromatopsia 3 Pathogenic:1
Pathogenic, no assertion criteria providedresearchMolecular Genetics Laboratory, Institute for Ophthalmic ResearchMar 27, 2017- -

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: rs1554609956; hg19: chr8-87638255; API