rs115246141

Variant names:

• chr8-86626069-A-C
• NM_019098.5:c.1492T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-86626069-A-C
• chr8-86626069-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_019098.5(CNGB3):​c.1492T>G​(p.Leu498Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNGB3 NM_019098.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

Genes affected

CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a topological_domain Extracellular (size 65) in uniprot entity CNGB3_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in NM_019098.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.1492T>G	p.Leu498Val	missense_variant	Exon 13 of 18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.1078T>G	p.Leu360Val	missense_variant	Exon 11 of 16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.1492T>G	p.Leu498Val	missense_variant	Exon 13 of 18	1	NM_019098.5	ENSP00000316605.5
CNGB3	ENST00000681546.1	n.1312T>G		non_coding_transcript_exon_variant	Exon 8 of 13
CNGB3	ENST00000681746.1	n.1492T>G		non_coding_transcript_exon_variant	Exon 13 of 19			ENSP00000505959.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459534 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726230

Gnomad4 AFR exome AF: 0.00

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.61	D
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.050	T
Polyphen		0.86	P
Vest4		0.42
MutPred		0.39		Loss of ubiquitination at K500 (P = 0.0982);
MVP		0.90
MPC		0.12
ClinPred		0.89	D
GERP RS		0.29
Varity_R		0.25
gMVP		0.58

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: chr8-87638297;