Variant X-41447942-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378477.3(NYX):c.22+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,205,233 control chromosomes in the GnomAD database, including 235 homozygotes. There are 8,352 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 19 hom., 477 hem., cov: 23)

Exomes 𝑓: 0.022 ( 216 hom. 7875 hem. )

Consequence

NYX
NM_001378477.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.666

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=-0.94).

BP6

Variant X-41447942-G-A is Benign according to our data. Variant chrX-41447942-G-A is described in ClinVar as [Benign]. Clinvar id is 1165274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0159 (1761/110893) while in subpopulation NFE AF= 0.0257 (1358/52904). AF 95% confidence interval is 0.0245. There are 19 homozygotes in gnomad4. There are 477 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYX	NM_001378477.3 linkuse as main transcript	c.22+16G>A		intron_variant		ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3 linkuse as main transcript	c.22+16G>A		intron_variant			NP_072089.2	Q9GZU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYX	ENST00000378220.3 linkuse as main transcript	c.22+16G>A		intron_variant		1	NM_001378477.3	ENSP00000367465.2		Q9GZU5
NYX	ENST00000342595.3 linkuse as main transcript	c.22+16G>A		intron_variant		1		ENSP00000340328.3		Q9GZU5

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

1761

AN:

110837

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

477

AN XY:

33043

show subpopulations

Gnomad AFR

AF:

0.00279

Gnomad AMI

AF:

0.00741

Gnomad AMR

AF:

0.00755

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00455

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.00603

GnomAD3 exomes

AF:

0.0164

AC:

2921

AN:

178653

Hom.:

AF XY:

0.0163

AC XY:

1043

AN XY:

63931

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00667

Gnomad ASJ exome

AF:

0.0205

Gnomad EAS exome

AF:

0.00445

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0235

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0222

AC:

24343

AN:

1094340

Hom.:

216

Cov.:

AF XY:

0.0219

AC XY:

7875

AN XY:

359854

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00661

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.00779

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0237

Gnomad4 NFE exome

AF:

0.0249

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0159

AC:

1761

AN:

110893

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

477

AN XY:

33109

show subpopulations

Gnomad4 AFR

AF:

0.00278

Gnomad4 AMR

AF:

0.00754

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.00485

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0257

Gnomad4 OTH

AF:

0.00596

Alfa

AF:

0.0181

Hom.:

172

Bravo

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.11

DANN

Benign

0.59

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