17-49206833-C-T

Position:

• chr17-49206833-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001198754.2(GNGT2):​c.134G>A​(p.Gly45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNGT2 NM_001198754.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.748

Genes affected

GNGT2 (HGNC:4412): (G protein subunit gamma transducin 2) Phototransduction in rod and cone photoreceptors is regulated by groups of signaling proteins. The encoded protein is thought to play a crucial role in cone phototransduction. It belongs to the G protein gamma family and localized specifically in cones. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0625557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNGT2	NM_001198754.2	c.134G>A	p.Gly45Glu	missense_variant	4/4	ENST00000507680.6
GNGT2	NM_001198755.1	c.134G>A	p.Gly45Glu	missense_variant	4/4
GNGT2	NM_001198756.1	c.134G>A	p.Gly45Glu	missense_variant	4/4
GNGT2	NM_031498.2	c.134G>A	p.Gly45Glu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNGT2	ENST00000507680.6	c.134G>A	p.Gly45Glu	missense_variant	4/4	4	NM_001198754.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.134G>A (p.G45E) alteration is located in exon 4 (coding exon 2) of the GNGT2 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the glycine (G) at amino acid position 45 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.011	.;T;T;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.68	T;.;.;.;.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.063	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.75	D;D;D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.45	N;N;N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.27	T;T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T;T
Polyphen		0.0020	.;B;B;B;B;B
Vest4		0.12
MutPred		0.35		Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);Gain of solvent accessibility (P = 0.024);
MVP		0.15
MPC		0.28
ClinPred		0.44	T
GERP RS		-0.87
Varity_R		0.079
gMVP		0.20

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: chr17-47284195;