11-6239234-A-T

Position:

• chr11-6239234-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037329.4(CNGA4):​c.28A>T​(p.Thr10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNGA4 NM_001037329.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0668281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA4	NM_001037329.4	c.28A>T	p.Thr10Ser	missense_variant	1/6	ENST00000379936.3	NP_001032406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA4	ENST00000379936.3	c.28A>T	p.Thr10Ser	missense_variant	1/6	1	NM_001037329.4	ENSP00000369268.2
CNGA4	ENST00000533426.5	c.-58-150A>T		intron_variant		2		ENSP00000433399.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727168

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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

Bravo AF: 0.00000756

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 27, 2023

The c.28A>T (p.T10S) alteration is located in exon 1 (coding exon 1) of the CNGA4 gene. This alteration results from a A to T substitution at nucleotide position 28, causing the threonine (T) at amino acid position 10 to be replaced by a serine (S). 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	0.083
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.067	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.22
Sift	Benign	0.65	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.13		Loss of glycosylation at T10 (P = 0.065);
MVP		0.74
MPC		0.21
ClinPred		0.048	T
GERP RS		3.0
Varity_R		0.037
gMVP		0.18

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

Other links and lift over

dbSNP: rs766223585; hg19: chr11-6260464;