NM_001377295.2:c.546G>A

Variant names:

• chr1-109606352-C-T
• rs1799875
• NM_001377295.2:c.546G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001377295.2(GNAT2):​c.546G>A​(p.Thr182Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,609,972 control chromosomes in the GnomAD database, including 162,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T182T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.37 (12575 hom., cov: 32)
  • Exomes 𝑓: 0.45 (149456 hom.)
• Consequence: GNAT2 NM_001377295.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.20
• Publications: 35 publications found

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 Gene-Disease associations (from GenCC):

• achromatopsia 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• GNAT2-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 1-109606352-C-T is Benign according to our data. Variant chr1-109606352-C-T is described in ClinVar as Benign. ClinVar VariationId is 259744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	NM_001377295.2	MANE Select	c.546G>A	p.Thr182Thr	synonymous	Exon 6 of 9	NP_001364224.1	P19087
	GNAT2	NM_001379232.1		c.546G>A	p.Thr182Thr	synonymous	Exon 6 of 9	NP_001366161.1	Q5T697
	GNAT2	NM_005272.5		c.546G>A	p.Thr182Thr	synonymous	Exon 5 of 8	NP_005263.1	P19087

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.546G>A	p.Thr182Thr	synonymous	Exon 6 of 9	ENSP00000505083.1	P19087
	GNAT2	ENST00000351050.8	TSL:1	c.546G>A	p.Thr182Thr	synonymous	Exon 5 of 8	ENSP00000251337.3	P19087
	GNAT2	ENST00000872462.1		c.546G>A	p.Thr182Thr	synonymous	Exon 6 of 10	ENSP00000542521.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55833 AN: 151818 Hom.: 12562 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.465 AC: 116935 AN: 251492 AF XY: 0.462

Gnomad AFR exome AF: 0.0971

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.437

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.511

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.445 AC: 648962 AN: 1458036 Hom.: 149456 Cov.: 31 AF XY: 0.444 AC XY: 322256 AN XY: 725592

African (AFR) AF: 0.0917 AC: 3068 AN: 33466

American (AMR) AF: 0.614 AC: 27474 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 11448 AN: 26108

East Asian (EAS) AF: 0.664 AC: 26359 AN: 39686

South Asian (SAS) AF: 0.402 AC: 34625 AN: 86178

European-Finnish (FIN) AF: 0.509 AC: 27165 AN: 53416

Middle Eastern (MID) AF: 0.498 AC: 2867 AN: 5758

European-Non Finnish (NFE) AF: 0.442 AC: 489695 AN: 1108426

Other (OTH) AF: 0.436 AC: 26261 AN: 60278

GnomAD4 genome AF: 0.368 AC: 55860 AN: 151936 Hom.: 12575 Cov.: 32 AF XY: 0.374 AC XY: 27785 AN XY: 74248

African (AFR) AF: 0.105 AC: 4360 AN: 41448

American (AMR) AF: 0.526 AC: 8039 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3275 AN: 5154

South Asian (SAS) AF: 0.386 AC: 1856 AN: 4810

European-Finnish (FIN) AF: 0.497 AC: 5232 AN: 10528

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30326 AN: 67944

Other (OTH) AF: 0.404 AC: 850 AN: 2106

Alfa AF: 0.421 Hom.: 28676

Bravo AF: 0.363

Asia WGS AF: 0.481 AC: 1670 AN: 3478

EpiCase AF: 0.448

EpiControl AF: 0.462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Achromatopsia 4 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	5.7
DANN	Benign	0.74
PhyloP100		-2.2
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1799875; hg19: chr1-110148974; COSMIC: COSV63554552; COSMIC: COSV63554552;