NM_144499.3:c.386A>G

Variant names:

• chr3-50193600-A-G
• rs786205854
• NM_144499.3:c.386A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_144499.3(GNAT1):​c.386A>G​(p.Asp129Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNAT1 NM_144499.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.08
• Publications: 8 publications found

Genes affected

GNAT1 (HGNC:4393): (G protein subunit alpha transducin 1) 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 rods. This gene is also expressed in other cells, and has been implicated in bitter taste transduction in rat taste cells. Mutations in this gene result in autosomal dominant congenital stationary night blindness. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2009]

GNAT1 Gene-Disease associations (from GenCC):

• congenital stationary night blindness autosomal dominant 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• inherited retinal dystrophy

  Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• retinal degeneration

  Inheritance: AR Classification: STRONG Submitted by: G2P
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital stationary night blindness 1G

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987
• PP5: Variant 3-50193600-A-G is Pathogenic according to our data. Variant chr3-50193600-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 190968.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144499.3. 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
	GNAT1	NM_144499.3	MANE Select	c.386A>G	p.Asp129Gly	missense	Exon 4 of 9	NP_653082.1	P11488
	GNAT1	NM_000172.4		c.386A>G	p.Asp129Gly	missense	Exon 4 of 9	NP_000163.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT1	ENST00000232461.8	TSL:5 MANE Select	c.386A>G	p.Asp129Gly	missense	Exon 4 of 9	ENSP00000232461.3	P11488
	GNAT1	ENST00000433068.5	TSL:5	c.386A>G	p.Asp129Gly	missense	Exon 4 of 9	ENSP00000387555.1	P11488
	GNAT1	ENST00000440836.1	TSL:3	c.242A>G	p.Asp81Gly	missense	Exon 4 of 5	ENSP00000403537.1	C9JCV8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital stationary night blindness 1G (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
PhyloP100		7.1
Varity_R		0.96
gMVP		0.95
Mutation Taster		=6/94	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs786205854; hg19: chr3-50231033;