rs1554614423

Positions:

• chr8-86671042-AGC-ATCACCAGGA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_019098.5(CNGB3):​c.393_394delinsTCCTGGTGA​(p.Gln131HisfsTer50) variant causes a frameshift change. 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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.31

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-86671043-GC-TCACCAGGA is Pathogenic according to our data. Variant chr8-86671043-GC-TCACCAGGA is described in ClinVar as [Pathogenic]. Clinvar id is 427649.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.393_394delinsTCCTGGTGA	p.Gln131HisfsTer50	frameshift_variant	4/18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.-22_-21delinsTCCTGGTGA		5_prime_UTR_variant	2/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.393_394delinsTCCTGGTGA	p.Gln131HisfsTer50	frameshift_variant	4/18	1	NM_019098.5	ENSP00000316605	P1
CNGB3	ENST00000680314.1	n.154_155delinsTCCTGGTGA		non_coding_transcript_exon_variant	2/3
CNGB3	ENST00000681746.1	c.393_394delinsTCCTGGTGA	p.Gln131HisfsTer50	frameshift_variant, NMD_transcript_variant	4/19			ENSP00000505959

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Achromatopsia 3 Pathogenic:1

Pathogenic, no assertion criteria provided

research

Molecular Genetics Laboratory, Institute for Ophthalmic Research

Mar 27, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554614423; hg19: chr8-87683271;