X-41447882-C-T

Variant names:

• chrX-41447882-C-T
• rs184823211
• NM_001378477.3:c.-23C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378477.3(NYX):​c.-23C>T 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 0.00000182 in 1,097,375 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: NYX NM_001378477.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• congenital stationary night blindness 1A

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• NYX-related retinopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High Hemizygotes in GnomAdExome4 at 2 AD,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378477.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYX	NM_001378477.3	MANE Select	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001365406.2	Q9GZU5
	NYX	NM_001378477.3	MANE Select	c.-23C>T		5_prime_UTR	Exon 2 of 3	NP_001365406.2	Q9GZU5
	NYX	NM_022567.3		c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_072089.2	Q9GZU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYX	ENST00000378220.3	TSL:1 MANE Select	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000367465.2	Q9GZU5
	NYX	ENST00000342595.3	TSL:1	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000340328.3	Q9GZU5
	NYX	ENST00000378220.3	TSL:1 MANE Select	c.-23C>T		5_prime_UTR	Exon 2 of 3	ENSP00000367465.2	Q9GZU5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097375 Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 2 AN XY: 362775

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35177

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19370

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53979

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40495

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841580

Other (OTH) AF: 0.0000217 AC: 1 AN: 46064

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		0.064
PromoterAI		0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs184823211; hg19: chrX-41307135;