Variant X-41447611-T-C 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.-294T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 389,488 control chromosomes in the GnomAD database, including 16,741 homozygotes. There are 43,412 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 ( 3731 hom., 10039 hem., cov: 23)

Exomes 𝑓: 0.37 ( 13010 hom. 33373 hem. )

Consequence

NYX
NM_022567.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.937

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=-0.85).

BP6

Variant X-41447611-T-C is Benign according to our data. Variant chrX-41447611-T-C is described in ClinVar as [Benign]. Clinvar id is 368266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
NYX	NM_001378477.3 link	c.-57+95T>C	intron_variant		ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3 link	c.-294T>C	5_prime_UTR_premature_start_codon_gain_variant	1/2		NP_072089.2	Q9GZU5
NYX	NM_022567.3 link	c.-294T>C	5_prime_UTR_variant	1/2		NP_072089.2	Q9GZU5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NYX	ENST00000342595 link	c.-294T>C	5_prime_UTR_premature_start_codon_gain_variant	1/2	1		ENSP00000340328.3	Q9GZU5
NYX	ENST00000342595 link	c.-294T>C	5_prime_UTR_variant	1/2	1		ENSP00000340328.3	Q9GZU5
NYX	ENST00000378220.3 link	c.-57+95T>C	intron_variant		1	NM_001378477.3	ENSP00000367465.2	Q9GZU5

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

32473

AN:

110680

Hom.:

3730

Cov.:

AF XY:

0.304

AC XY:

10011

AN XY:

32956

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.366

AC:

101933

AN:

278751

Hom.:

13010

Cov.:

AF XY:

0.396

AC XY:

33373

AN XY:

84361

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.384

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.293

AC:

32496

AN:

110737

Hom.:

3731

Cov.:

AF XY:

0.304

AC XY:

10039

AN XY:

33021

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.300

Hom.:

12408

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

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

-0.85

CADD

Benign

DANN

Benign

0.70

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