X-41473479-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001378477.3(NYX):​c.23-12C>G 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 858,707 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: NYX NM_001378477.3 intron
• Scores: Splicing: ADA: 0.0006662
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-41473479-C-G is Benign according to our data. Variant chrX-41473479-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1672638.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.23-12C>G		intron	N/A	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.23-12C>G		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>G		intron	N/A	ENSP00000367465.2	Q9GZU5
	NYX	ENST00000342595.3	TSL:1	c.23-12C>G		intron	N/A	ENSP00000340328.3	Q9GZU5
	NYX	ENST00000938151.1		c.23-12C>G		intron	N/A	ENSP00000608210.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 858707 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 259429

African (AFR) AF: 0.0000577 AC: 1 AN: 17323

American (AMR) AF: 0.00 AC: 0 AN: 6111

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10608

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 26176

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: 722505

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

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.46
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00067
dbscSNV1_RF	Benign	0.072
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

Other links and lift over

dbSNP: rs1355344476; hg19: chrX-41332732;