chr1-109610108-G-C

Variant names:

• chr1-109610108-G-C
• rs121434585
• NM_001377295.2:c.235C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001377295.2(GNAT2):​c.235C>G​(p.Gln79Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNAT2 NM_001377295.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	NM_001377295.2	MANE Select	c.235C>G	p.Gln79Glu	missense	Exon 4 of 9	NP_001364224.1
	GNAT2	NM_001379232.1		c.235C>G	p.Gln79Glu	missense	Exon 4 of 9	NP_001366161.1
	GNAT2	NM_005272.5		c.235C>G	p.Gln79Glu	missense	Exon 3 of 8	NP_005263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.235C>G	p.Gln79Glu	missense	Exon 4 of 9	ENSP00000505083.1
	GNAT2	ENST00000351050.8	TSL:1	c.235C>G	p.Gln79Glu	missense	Exon 3 of 8	ENSP00000251337.3
	GNAT2	ENST00000622865.1	TSL:3	c.235C>G	p.Gln79Glu	missense	Exon 4 of 5	ENSP00000482596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.7	L
PhyloP100		9.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.20	T
Polyphen		0.89	P
Vest4		0.72
MutPred		0.64		Loss of catalytic residue at Q79 (P = 0.1297)
MVP		0.92
MPC		0.35
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.61
gMVP		0.64
Mutation Taster		=54/46	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: rs121434585; hg19: chr1-110152730;