NM_001377295.2:c.909A>C

Variant names:

• chr1-109603510-T-G
• rs1309275044
• NM_001377295.2:c.909A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377295.2(GNAT2):​c.909A>C​(p.Ile303Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,260 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GNAT2 NM_001377295.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

GNAT2 Gene-Disease associations (from GenCC):

• achromatopsia 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• GNAT2-related retinopathy

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377295.2. 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
	GNAT2	NM_001377295.2	MANE Select	c.909A>C	p.Ile303Ile	synonymous	Exon 9 of 9	NP_001364224.1	P19087
	GNAT2	NM_001379232.1		c.909A>C	p.Ile303Ile	synonymous	Exon 9 of 9	NP_001366161.1	Q5T697
	GNAT2	NM_005272.5		c.909A>C	p.Ile303Ile	synonymous	Exon 8 of 8	NP_005263.1	P19087

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.909A>C	p.Ile303Ile	synonymous	Exon 9 of 9	ENSP00000505083.1	P19087
	GNAT2	ENST00000351050.8	TSL:1	c.909A>C	p.Ile303Ile	synonymous	Exon 8 of 8	ENSP00000251337.3	P19087
	GNAT2	ENST00000872462.1		c.909A>C	p.Ile303Ile	synonymous	Exon 9 of 10	ENSP00000542521.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		4.0
Mutation Taster		=88/12	polymorphism

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: rs1309275044; hg19: chr1-110146132;