chrX-41473507-GC-G

Variant names:

• chrX-41473507-GC-G
• NM_001378477.3:c.42delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001378477.3(NYX):​c.42delC​(p.Ser15AlafsTer121) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: NYX NM_001378477.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.46
• Publications: 0 publications found

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: G2P, Labcorp Genetics (formerly Invitae)
• NYX-related retinopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 12 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 55 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-41473507-GC-G is Pathogenic according to our data. Variant chrX-41473507-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 3643766.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378477.3. 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
	NYX	NM_001378477.3	MANE Select	c.42delC	p.Ser15AlafsTer121	frameshift	Exon 3 of 3	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.42delC	p.Ser15AlafsTer121	frameshift	Exon 2 of 2	NP_072089.2	Q9GZU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYX	ENST00000378220.3	TSL:1 MANE Select	c.42delC	p.Ser15AlafsTer121	frameshift	Exon 3 of 3	ENSP00000367465.2	Q9GZU5
	NYX	ENST00000342595.3	TSL:1	c.42delC	p.Ser15AlafsTer121	frameshift	Exon 2 of 2	ENSP00000340328.3	Q9GZU5
	NYX	ENST00000938151.1		c.42delC	p.Ser15AlafsTer121	frameshift	Exon 3 of 3	ENSP00000608210.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 873659 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 265031

African (AFR) AF: 0.00 AC: 0 AN: 17584

American (AMR) AF: 0.00 AC: 0 AN: 7069

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11156

East Asian (EAS) AF: 0.00 AC: 0 AN: 18764

South Asian (SAS) AF: 0.00 AC: 0 AN: 29006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21287

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2159

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 731194

Other (OTH) AF: 0.00 AC: 0 AN: 35440

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chrX-41332760;