11-6239785-A-G

Position:

• chr11-6239785-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037329.4(CNGA4):​c.266A>G​(p.His89Arg) 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. 12/21 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: CNGA4 NM_001037329.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.862

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13684699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA4	NM_001037329.4	c.266A>G	p.His89Arg	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.266A>G	p.His89Arg	missense_variant	3/6	1	NM_001037329.4	ENSP00000369268.2
CNGA4	ENST00000533426.5	c.146A>G	p.His49Arg	missense_variant	3/5	2		ENSP00000433399.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 07, 2022

The c.266A>G (p.H89R) alteration is located in exon 3 (coding exon 3) of the CNGA4 gene. This alteration results from a A to G substitution at nucleotide position 266, causing the histidine (H) at amino acid position 89 to be replaced by an arginine (R). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	17
DANN	Benign	0.39
DEOGEN2	Benign	0.0081	T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.20	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	-0.47	.;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.70	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.84	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0060	B;B
Vest4		0.14
MutPred		0.67		.;Gain of helix (P = 0.0425);
MVP		0.71
MPC		0.36
ClinPred		0.53	D
GERP RS		5.3
Varity_R		0.19
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: chr11-6261015; COSMIC: COSV104699289;