X-41473506-T-G

Position:

• chrX-41473506-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001378477.3(NYX):​c.38T>G​(p.Leu13Arg) 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: 4.59

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYX	NM_001378477.3	c.38T>G	p.Leu13Arg	missense_variant	3/3	ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3	c.38T>G	p.Leu13Arg	missense_variant	2/2		NP_072089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYX	ENST00000378220.3	c.38T>G	p.Leu13Arg	missense_variant	3/3	1	NM_001378477.3	ENSP00000367465.2
NYX	ENST00000342595.3	c.38T>G	p.Leu13Arg	missense_variant	2/2	1		ENSP00000340328.3
NYX	ENST00000486842.1	n.291T>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.53T>G (p.L18R) alteration is located in exon 2 (coding exon 2) of the NYX gene. This alteration results from a T to G substitution at nucleotide position 53, causing the leucine (L) at amino acid position 18 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.49	.;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.99	D;D
Vest4		0.75
MutPred		0.65		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.97
MPC		2.2
ClinPred		0.79	D
GERP RS		3.5
Varity_R		0.35
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-41332759;