chr1-109608773-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377295.2(GNAT2):c.319C>A(p.Leu107Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,613,600 control chromosomes in the GnomAD database, including 2,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L107V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.031 ( 238 hom., cov: 32)

Exomes 𝑓: 0.036 ( 2217 hom. )

Consequence

GNAT2
NM_001377295.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.06

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016860664).

BP6

Variant 1-109608773-G-T is Benign according to our data. Variant chr1-109608773-G-T is described in ClinVar as [Benign]. Clinvar id is 259743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAT2	NM_001377295.2 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 5 of 9	ENST00000679935.1	NP_001364224.1
GNAT2	NM_001379232.1 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 5 of 9		NP_001366161.1
GNAT2	NM_005272.5 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 4 of 8		NP_005263.1	P19087Q5T697

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GNAT2	ENST00000679935.1 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 5 of 9		NM_001377295.2	ENSP00000505083.1	P19087
GNAT2	ENST00000351050.8 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 4 of 8	1		ENSP00000251337.3	P19087
GNAT2	ENST00000622865.1 link	c.319C>A	p.Leu107Ile	missense_variant	Exon 5 of 5	3		ENSP00000482596.1	A0A087WZE5

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4682

AN:

152160

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0225

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0504

AC:

12664

AN:

251434

Hom.:

779

AF XY:

0.0524

AC XY:

7127

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00591

Gnomad AMR exome

AF:

0.0297

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0355

AC:

51912

AN:

1461322

Hom.:

2217

Cov.:

AF XY:

0.0376

AC XY:

27353

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.0258

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0308

AC:

4685

AN:

152278

Hom.:

238

Cov.:

AF XY:

0.0341

AC XY:

2536

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0225

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0277

Hom.:

268

Bravo

AF:

0.0280

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.0235

AC:

202

ExAC

AF:

0.0501

AC:

6081

Asia WGS

AF:

0.144

AC:

498

AN:

3478

EpiCase

AF:

0.0243

EpiControl

AF:

0.0245

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Achromatopsia 4

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0017

T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

0.70

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.50

N;.

REVEL

Uncertain

0.35

Sift

Benign

0.063

T;.

Sift4G

Benign

0.37

T;.

Polyphen

1.0

D;.

Vest4

0.24

MPC

0.53

ClinPred

0.078

GERP RS

4.5

Varity_R

0.31

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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