11-6239746-G-A

Position:

• chr11-6239746-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001037329.4(CNGA4):​c.227G>A​(p.Ser76Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNGA4 NM_001037329.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA4	NM_001037329.4	c.227G>A	p.Ser76Asn	missense_variant	3/6	ENST00000379936.3	NP_001032406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA4	ENST00000379936.3	c.227G>A	p.Ser76Asn	missense_variant	3/6	1	NM_001037329.4	ENSP00000369268.2
CNGA4	ENST00000533426.5	c.107G>A	p.Ser36Asn	missense_variant	3/5	2		ENSP00000433399.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.227G>A (p.S76N) alteration is located in exon 3 (coding exon 3) of the CNGA4 gene. This alteration results from a G to A substitution at nucleotide position 227, causing the serine (S) at amino acid position 76 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	0.77
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.9	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D;T
Sift4G	Uncertain	0.011	D;T
Polyphen		0.97	D;P
Vest4		0.51
MutPred		0.63		.;Loss of stability (P = 0.1437);
MVP		0.86
MPC		0.29
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.62

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: chr11-6260976;