X-41473500-T-A

Variant names:

• chrX-41473500-T-A
• rs2064370785
• NM_001378477.3:c.32T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001378477.3(NYX):​c.32T>A​(p.Leu11His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NYX NM_001378477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

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.32T>A	p.Leu11His	missense	Exon 3 of 3	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.32T>A	p.Leu11His	missense	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.32T>A	p.Leu11His	missense	Exon 3 of 3	ENSP00000367465.2	Q9GZU5
	NYX	ENST00000342595.3	TSL:1	c.32T>A	p.Leu11His	missense	Exon 2 of 2	ENSP00000340328.3	Q9GZU5
	NYX	ENST00000938151.1		c.32T>A	p.Leu11His	missense	Exon 3 of 3	ENSP00000608210.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Uncertain	0.48	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.73
MutPred		0.56		Gain of catalytic residue at G17 (P = 0.0516)
MVP		0.97
MPC		1.1
ClinPred		0.64	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.63
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs2064370785; hg19: chrX-41332753;