3-50194111-CAG-GAA

Variant names:

• chr3-50194111-CAG-GAA
• NM_144499.3:c.598_600delCAGinsGAA
• GNAT1 p.Gln200Glu

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_144499.3(GNAT1):​c.598_600delCAGinsGAA​(p.Gln200Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNAT1 NM_144499.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.88
• Publications: 0 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: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_144499.3 (GNAT1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.598_600delCAGinsGAA	p.Gln200Glu	missense	N/A	NP_653082.1	P11488
	GNAT1	NM_000172.4		c.598_600delCAGinsGAA	p.Gln200Glu	missense	N/A	NP_000163.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT1	ENST00000232461.8	TSL:5 MANE Select	c.598_600delCAGinsGAA	p.Gln200Glu	missense	N/A	ENSP00000232461.3	P11488
	GNAT1	ENST00000433068.5	TSL:5	c.598_600delCAGinsGAA	p.Gln200Glu	missense	N/A	ENSP00000387555.1	P11488
	GNAT1	ENST00000481246.1	TSL:3	n.265_267delCAGinsGAA		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

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

hg19: chr3-50231544;