chrX-41473525-G-C

Position:

• chrX-41473525-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001378477.3(NYX):​c.57G>C​(p.Val19Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 882,566 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.00012 (0 hom. 30 hem.)
• Consequence: NYX NM_001378477.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.333

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant X-41473525-G-C is Benign according to our data. Variant chrX-41473525-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1640395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.333 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 30 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NYX	NM_001378477.3	c.57G>C	p.Val19Val	synonymous_variant	3/3	ENST00000378220.3	NP_001365406.2
NYX	NM_022567.3	c.57G>C	p.Val19Val	synonymous_variant	2/2		NP_072089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NYX	ENST00000378220.3	c.57G>C	p.Val19Val	synonymous_variant	3/3	1	NM_001378477.3	ENSP00000367465.2
NYX	ENST00000342595.3	c.57G>C	p.Val19Val	synonymous_variant	2/2	1		ENSP00000340328.3
NYX	ENST00000486842.1	n.310G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.000121 AC: 107 AN: 882566 Hom.: 0 Cov.: 23 AF XY: 0.000113 AC XY: 30 AN XY: 266192

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: 0.000146

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs1054600525; hg19: chrX-41332778;