dbSNP rs104894911: NYX:p.Ile96Thr (chrX-41473755-T-C) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001378477.3(NYX):c.287T>C(p.Ile96Thr) 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

NYX
NM_001378477.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.03

Publications

1 publications found

Variant links:

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

NYX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.983

PP5

Variant X-41473755-T-C is Pathogenic according to our data. Variant chrX-41473755-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 11425.Status of the report is no_assertion_criteria_provided, 0 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.287T>C	p.Ile96Thr	missense	Exon 3 of 3	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.287T>C	p.Ile96Thr	missense	Exon 2 of 2	NP_072089.2	Q9GZU5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NYX	ENST00000378220.3	TSL:1 MANE Select	c.287T>C	p.Ile96Thr	missense	Exon 3 of 3	ENSP00000367465.2	Q9GZU5
NYX	ENST00000342595.3	TSL:1	c.287T>C	p.Ile96Thr	missense	Exon 2 of 2	ENSP00000340328.3	Q9GZU5
NYX	ENST00000938151.1		c.287T>C	p.Ile96Thr	missense	Exon 3 of 3	ENSP00000608210.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1041882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

336092

African (AFR)

AF:

0.00

AC:

AN:

22892

American (AMR)

AF:

0.00

AC:

AN:

30765

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17720

East Asian (EAS)

AF:

0.00

AC:

AN:

25837

South Asian (SAS)

AF:

0.00

AC:

AN:

49911

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3977

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

819871

Other (OTH)

AF:

0.00

AC:

AN:

43627

GnomAD4 genome

Cov.:

Alfa

AF:

0.000671

Hom.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital stationary night blindness 1A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.81

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.2

PhyloP100

6.0

PrimateAI

Pathogenic

0.97

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.87

MutPred

0.92

Loss of stability (P = 9e-04)

MVP

0.99

MPC

2.1

ClinPred

0.99

GERP RS

5.0

Varity_R

0.96

gMVP

0.88

Mutation Taster

=11/89

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over