2-98369976-A-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001298.3(CNGA3):​c.1A>T​(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

CNGA3
NM_001298.3 initiator_codon

Scores

7
4
5

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.61
Variant links:
Genes affected
CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Start lost variant, next in-frame start position is after 10 pathogenic variants. Next in-frame start position is after 153 CDS bases. Genomic position: 98377738. Lost 0.073 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNGA3NM_001298.3 linkc.1A>T p.Met1? initiator_codon_variant Exon 2 of 8 ENST00000272602.7 NP_001289.1 Q16281-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNGA3ENST00000272602.7 linkc.1A>T p.Met1? initiator_codon_variant Exon 2 of 8 1 NM_001298.3 ENSP00000272602.2 Q16281-1
CNGA3ENST00000436404.6 linkc.1A>T p.Met1? initiator_codon_variant Exon 2 of 7 1 ENSP00000410070.2 Q16281-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

Achromatopsia 2 Uncertain:1
Apr 15, 2021
Molecular Genetics Laboratory, Institute for Ophthalmic Research
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.50
CADD
Benign
22
DANN
Uncertain
0.97
DEOGEN2
Benign
0.16
T;.;T
Eigen
Benign
-0.051
Eigen_PC
Benign
0.061
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D;D;.
M_CAP
Pathogenic
0.90
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Uncertain
0.69
D
PROVEAN
Benign
-1.0
N;N;N
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.031
B;.;B
Vest4
0.93
MutPred
0.99
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
0.92
ClinPred
0.87
D
GERP RS
4.1
Varity_R
0.91
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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: rs1324338876; hg19: chr2-98986439; API