rs41280330

Positions:

• chr1-109608722-C-G
• chr1-109608722-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001377295.2(GNAT2):​c.370G>C​(p.Val124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAT2	NM_001377295.2	c.370G>C	p.Val124Leu	missense_variant	5/9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1	c.370G>C	p.Val124Leu	missense_variant	5/9		NP_001366161.1
GNAT2	NM_005272.5	c.370G>C	p.Val124Leu	missense_variant	4/8		NP_005263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAT2	ENST00000679935.1	c.370G>C	p.Val124Leu	missense_variant	5/9		NM_001377295.2	ENSP00000505083	P1
GNAT2	ENST00000351050.8	c.370G>C	p.Val124Leu	missense_variant	4/8	1		ENSP00000251337	P1
GNAT2	ENST00000622865.1	c.370G>C	p.Ter124=	incomplete_terminal_codon_variant, coding_sequence_variant	5/5	3		ENSP00000482596

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.0026
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.31	N
MutationTaster	Benign	0.85	D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.26	N
REVEL	Uncertain	0.30
Sift	Benign	0.71	T
Sift4G	Benign	0.54	T
Polyphen		0.16	B
Vest4		0.38
MutPred		0.69		Gain of catalytic residue at V124 (P = 0.0568);
MVP		0.86
MPC		0.37
ClinPred		0.48	T
GERP RS		4.7
Varity_R		0.24
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41280330; hg19: chr1-110151344;