Variant 17-49206860-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001198754.2(GNGT2):c.107T>C(p.Ile36Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GNGT2
NM_001198754.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.78

Variant links:

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]

GNGT2 links:

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ACMG classification

Classification made for transcript

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
GNGT2	NM_001198754.2 linkuse as main transcript	c.107T>C	p.Ile36Thr	missense_variant	4/4	ENST00000507680.6
GNGT2	NM_001198755.1 linkuse as main transcript	c.107T>C	p.Ile36Thr	missense_variant	4/4
GNGT2	NM_001198756.1 linkuse as main transcript	c.107T>C	p.Ile36Thr	missense_variant	4/4
GNGT2	NM_031498.2 linkuse as main transcript	c.107T>C	p.Ile36Thr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNGT2	ENST00000507680.6 linkuse as main transcript	c.107T>C	p.Ile36Thr	missense_variant	4/4	4	NM_001198754.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251278

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.107T>C (p.I36T) alteration is located in exon 4 (coding exon 2) of the GNGT2 gene. This alteration results from a T to C substitution at nucleotide position 107, causing the isoleucine (I) at amino acid position 36 to be replaced by a threonine (T). 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

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;T;T;T;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.56

T;.;.;.;.;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.66

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T

Polyphen

0.20

.;B;B;B;B;B

Vest4

0.84

MutPred

0.74

Gain of ubiquitination at K31 (P = 0.0435);Gain of ubiquitination at K31 (P = 0.0435);Gain of ubiquitination at K31 (P = 0.0435);Gain of ubiquitination at K31 (P = 0.0435);Gain of ubiquitination at K31 (P = 0.0435);Gain of ubiquitination at K31 (P = 0.0435);

MVP

0.24

MPC

0.73

ClinPred

0.96

GERP RS

4.8

Varity_R

0.25

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over