Genetic Variant NM_001378477.3:c.287T>C (chrX-41473755-T-C) – ACMG Classification: Likely_pathogenic (7 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 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 id is 11425.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYX	NM_001378477.3 link	c.287T>C	p.Ile96Thr	missense_variant	Exon 3 of 3	ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3 link	c.287T>C	p.Ile96Thr	missense_variant	Exon 2 of 2		NP_072089.2	Q9GZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NYX	ENST00000378220.3 link	c.287T>C	p.Ile96Thr	missense_variant	Exon 3 of 3	1	NM_001378477.3	ENSP00000367465.2	Q9GZU5
NYX	ENST00000342595.3 link	c.287T>C	p.Ile96Thr	missense_variant	Exon 2 of 2	1		ENSP00000340328.3	Q9GZU5
NYX	ENST00000486842.1 link	n.*46T>C		downstream_gene_variant		3

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Congenital stationary night blindness 1A

Pathogenic:1

Jan 01, 2006

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

.;T

M_CAP

Pathogenic

0.81

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Pathogenic

0.97

PROVEAN

Uncertain

-4.2

D;D

REVEL

Pathogenic

0.82

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.87

MutPred

0.92

Loss of stability (P = 9e-04);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over