NM_001378477.3:c.90C>A

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001378477.3(NYX):c.90C>A(p.Cys30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 899,690 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. C30C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000022 ( 0 hom. 0 hem. )

Consequence

NYX
NM_001378477.3 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 0.694

Publications

1 publications found

Variant links:

Genes affected

NYX (HGNC:8082): (nyctalopin) The product of this gene belongs to the small leucine-rich proteoglycan (SLRP) family of proteins. Defects in this gene are the cause of congenital stationary night blindness type 1 (CSNB1), also called X-linked congenital stationary night blindness (XLCSNB). CSNB1 is a rare inherited retinal disorder characterized by impaired scotopic vision, myopia, hyperopia, nystagmus and reduced visual acuity. The role of other SLRP proteins suggests that mutations in this gene disrupt developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB. [provided by RefSeq, Oct 2008]

NYX Gene-Disease associations (from GenCC):

congenital stationary night blindness 1A
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
NYX-related retinopathy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NYX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 52 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-41473558-C-A is Pathogenic according to our data. Variant chrX-41473558-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 11422.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYX	NM_001378477.3 link	c.90C>A	p.Cys30*	stop_gained	Exon 3 of 3	ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3 link	c.90C>A	p.Cys30*	stop_gained	Exon 2 of 2		NP_072089.2	Q9GZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NYX	ENST00000378220.3 link	c.90C>A	p.Cys30*	stop_gained	Exon 3 of 3	1	NM_001378477.3	ENSP00000367465.2	Q9GZU5
NYX	ENST00000342595.3 link	c.90C>A	p.Cys30*	stop_gained	Exon 2 of 2	1		ENSP00000340328.3	Q9GZU5
NYX	ENST00000486842.1 link	n.343C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000222

AC:

AN:

899690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

273356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18006

American (AMR)

AF:

0.00

AC:

AN:

9397

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12342

East Asian (EAS)

AF:

0.00

AC:

AN:

18721

South Asian (SAS)

AF:

0.00

AC:

AN:

33752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2800

European-Non Finnish (NFE)

AF:

0.00000134

AC:

AN:

745162

Other (OTH)

AF:

0.0000272

AC:

AN:

36774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Congenital stationary night blindness 1A

Pathogenic:1

Nov 01, 2000

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.71

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Uncertain

0.82

PhyloP100

0.69

Vest4

0.66

GERP RS

2.8

Mutation Taster

=12/188

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over