11-6239473-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001037329.4(CNGA4):​c.152T>A​(p.Ile51Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,858 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CNGA4
NM_001037329.4 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57
Variant links:
Genes affected
CNGA4 (HGNC:2152): (cyclic nucleotide gated channel subunit alpha 4) CNGA4 is a modulatory subunit of vertebrate cyclic nucleotide-gated membrane channels that transduce odorant signals (Munger et al., 2001 [PubMed 11739959]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CNGA4NM_001037329.4 linkc.152T>A p.Ile51Asn missense_variant 2/6 ENST00000379936.3 NP_001032406.1 Q8IV77-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNGA4ENST00000379936.3 linkc.152T>A p.Ile51Asn missense_variant 2/61 NM_001037329.4 ENSP00000369268.2 Q8IV77-1
CNGA4ENST00000533426.5 linkc.32T>A p.Ile11Asn missense_variant 2/52 ENSP00000433399.1 B4DYQ8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251492
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 22, 2023The c.152T>A (p.I51N) alteration is located in exon 2 (coding exon 2) of the CNGA4 gene. This alteration results from a T to A substitution at nucleotide position 152, causing the isoleucine (I) at amino acid position 51 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.031
T;D
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Pathogenic
0.48
D
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.95
N;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.99
D;D
Vest4
0.60
MutPred
0.43
.;Loss of stability (P = 0.0666);
MVP
0.95
MPC
1.1
ClinPred
0.89
D
GERP RS
5.7
Varity_R
0.74
gMVP
0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1248241229; hg19: chr11-6260703; API