rs786205854

Positions:

• chr3-50193600-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 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 id is 190968.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-50193600-A-G is described in Lovd as [Pathogenic]. Variant chr3-50193600-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAT1	NM_144499.3	c.386A>G	p.Asp129Gly	missense_variant	4/9	ENST00000232461.8	NP_653082.1
GNAT1	NM_000172.4	c.386A>G	p.Asp129Gly	missense_variant	4/9		NP_000163.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAT1	ENST00000232461.8	c.386A>G	p.Asp129Gly	missense_variant	4/9	5	NM_144499.3	ENSP00000232461	P1
GNAT1	ENST00000433068.5	c.386A>G	p.Asp129Gly	missense_variant	4/9	5		ENSP00000387555	P1
GNAT1	ENST00000440836.1	c.242A>G	p.Asp81Gly	missense_variant	4/5	3		ENSP00000403537
GNAT1	ENST00000481246.1	n.29A>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital stationary night blindness 1G Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 13, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.94	D;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.99	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.4	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.8	D;D;D
REVEL	Pathogenic	0.95
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.99
MutPred		0.89		Gain of MoRF binding (P = 0.0368);Gain of MoRF binding (P = 0.0368);.;
MVP		0.99
MPC		1.9
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.96
gMVP		0.95

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

Other links and lift over

dbSNP: rs786205854; hg19: chr3-50231033;