Variant X-41447576-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022567.3(NYX):c.-329A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 349,570 control chromosomes in the GnomAD database, including 15,207 homozygotes. There are 37,161 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 3729 hom., 9812 hem., cov: 22)

Exomes 𝑓: 0.37 ( 11478 hom. 27349 hem. )

Consequence

NYX
NM_022567.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.187

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-41447576-A-G is Benign according to our data. Variant chrX-41447576-A-G is described in ClinVar as [Benign]. Clinvar id is 368265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYX	NM_001378477.3 linkuse as main transcript	c.-57+60A>G		intron_variant		ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3 linkuse as main transcript	c.-329A>G		5_prime_UTR_variant	1/2		NP_072089.2	Q9GZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYX	ENST00000342595 linkuse as main transcript	c.-329A>G		5_prime_UTR_variant	1/2	1		ENSP00000340328.3		Q9GZU5
NYX	ENST00000378220.3 linkuse as main transcript	c.-57+60A>G		intron_variant		1	NM_001378477.3	ENSP00000367465.2		Q9GZU5

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

32260

AN:

109771

Hom.:

3728

Cov.:

AF XY:

0.305

AC XY:

9784

AN XY:

32097

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.365

AC:

87534

AN:

239740

Hom.:

11478

Cov.:

AF XY:

0.395

AC XY:

27349

AN XY:

69164

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.385

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.549

Gnomad4 SAS exome

AF:

0.578

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.294

AC:

32283

AN:

109830

Hom.:

3729

Cov.:

AF XY:

0.305

AC XY:

9812

AN XY:

32164

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.319

Hom.:

13432

Bravo

AF:

0.281

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital stationary night blindness 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.74

DANN

Benign

0.74

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