chr4-47936488-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001379270.1(CNGA1):​c.1994T>C​(p.Leu665Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CNGA1
NM_001379270.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81
Variant links:
Genes affected
CNGA1 (HGNC:2148): (cyclic nucleotide gated channel subunit alpha 1) The protein encoded by this gene is involved in phototransduction. Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. This represents the last step in the phototransduction pathway. Defects in this gene are a cause of retinitis pigmentosa autosomal recessive (ARRP) disease. Multiple transcript variants have been found for this gene. [provided by RefSeq, Oct 2019]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12559506).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CNGA1NM_001379270.1 linkuse as main transcriptc.1994T>C p.Leu665Pro missense_variant 11/11 ENST00000514170.7 NP_001366199.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNGA1ENST00000514170.7 linkuse as main transcriptc.1994T>C p.Leu665Pro missense_variant 11/115 NM_001379270.1 ENSP00000426862.3 P29973

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitterresearchDept Of Ophthalmology, Nagoya UniversityOct 01, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Uncertain
0.040
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.062
.;T;.;T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.59
.;.;T;T;.
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Uncertain
0.071
D
MutationAssessor
Benign
1.7
.;L;.;L;L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.93
N;N;.;N;N
REVEL
Benign
0.28
Sift
Benign
0.093
T;T;.;T;T
Sift4G
Benign
0.22
T;T;T;T;T
Polyphen
0.0
.;B;.;B;B
Vest4
0.30
MutPred
0.46
.;Gain of disorder (P = 0.0098);.;Gain of disorder (P = 0.0098);Gain of disorder (P = 0.0098);
MVP
0.92
MPC
0.18
ClinPred
0.18
T
GERP RS
4.5
Varity_R
0.18
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-47938505; API