1-109610108-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAT2	NM_001377295.2	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 9		NP_001366161.1
GNAT2	NM_005272.5	c.235C>G	p.Gln79Glu	missense_variant	Exon 3 of 8		NP_005263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAT2	ENST00000679935.1	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 9		NM_001377295.2	ENSP00000505083.1
GNAT2	ENST00000351050.8	c.235C>G	p.Gln79Glu	missense_variant	Exon 3 of 8	1		ENSP00000251337.3
GNAT2	ENST00000622865.1	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 5	3		ENSP00000482596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.7	L;.
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);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

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: chr1-110152730;