chrX-41473479-C-A

Variant names:

• chrX-41473479-C-A
• rs1355344476
• NM_001378477.3:c.23-12C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378477.3(NYX):​c.23-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 858,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: NYX NM_001378477.3 intron
• Scores: Splicing: ADA: 0.0001551
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.23-12C>A		intron	N/A	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.23-12C>A		intron	N/A	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.23-12C>A		intron	N/A	ENSP00000367465.2	Q9GZU5
	NYX	ENST00000342595.3	TSL:1	c.23-12C>A		intron	N/A	ENSP00000340328.3	Q9GZU5
	NYX	ENST00000938151.1		c.23-12C>A		intron	N/A	ENSP00000608210.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 858699 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 259419

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17325

American (AMR) AF: 0.00 AC: 0 AN: 6110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10607

East Asian (EAS) AF: 0.00 AC: 0 AN: 18712

South Asian (SAS) AF: 0.0000382 AC: 1 AN: 26173

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20559

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2053

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 722500

Other (OTH) AF: 0.00 AC: 0 AN: 34660

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.70
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.022
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

dbSNP: rs1355344476; hg19: chrX-41332732;