rs104893616
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_001298.3(CNGA3):āc.872C>Gā(p.Thr291Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 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 Pathogenic (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
CNGA3
NM_001298.3 missense
NM_001298.3 missense
Scores
14
4
1
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a helix (size 13) in uniprot entity CNGA3_HUMAN there are 16 pathogenic changes around while only 0 benign (100%) in NM_001298.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.952
PP5
?
Variant 2-98396042-C-G is Pathogenic according to our data. Variant chr2-98396042-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 9477.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98396042-C-G is described in Lovd as [Likely_pathogenic]. Variant chr2-98396042-C-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNGA3 | NM_001298.3 | c.872C>G | p.Thr291Arg | missense_variant | 8/8 | ENST00000272602.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGA3 | ENST00000272602.7 | c.872C>G | p.Thr291Arg | missense_variant | 8/8 | 1 | NM_001298.3 | A1 | |
CNGA3 | ENST00000436404.6 | c.818C>G | p.Thr273Arg | missense_variant | 7/7 | 1 | P4 | ||
CNGA3 | ENST00000409937.1 | n.1025C>G | non_coding_transcript_exon_variant | 8/8 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727244
GnomAD4 exome
AF:
AC:
2
AN:
1461886
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727244
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ESP6500AA
AF:
AC:
0
ESP6500EA
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1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Achromatopsia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1998 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Nov 28, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M;.
MutationTaster
Benign
A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at