NM_001298.3:c.-65G>T

Variant names:

• chr2-98346507-G-T
• rs750494086
• NM_001298.3:c.-65G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001298.3(CNGA3):​c.-65G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000406 in 246,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CNGA3 NM_001298.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 0 publications found

Genes affected

CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CNGA3 Gene-Disease associations (from GenCC):

• achromatopsia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae)
• CNGA3-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000222000 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001298.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	NM_001298.3	MANE Select	c.-65G>T		5_prime_UTR	Exon 1 of 8	NP_001289.1	Q16281-1
	CNGA3	NM_001079878.2		c.-65G>T		5_prime_UTR	Exon 1 of 7	NP_001073347.1	Q16281-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	ENST00000272602.7	TSL:1 MANE Select	c.-65G>T		5_prime_UTR	Exon 1 of 8	ENSP00000272602.2	Q16281-1
	CNGA3	ENST00000436404.6	TSL:1	c.-65G>T		5_prime_UTR	Exon 1 of 7	ENSP00000410070.2	Q16281-2
	CNGA3	ENST00000853268.1		c.-65G>T		5_prime_UTR	Exon 1 of 9	ENSP00000523327.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000406 AC: 1 AN: 246192 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124806

African (AFR) AF: 0.00 AC: 0 AN: 7174

American (AMR) AF: 0.000135 AC: 1 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9230

East Asian (EAS) AF: 0.00 AC: 0 AN: 22886

South Asian (SAS) AF: 0.00 AC: 0 AN: 3030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 157954

Other (OTH) AF: 0.00 AC: 0 AN: 16360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.80
PhyloP100		-0.33
PromoterAI		-0.0027	Neutral

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

Other links and lift over

dbSNP: rs750494086; hg19: chr2-98962970;