rs3747350

chrX-43949084-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000266.4(NDP):c.*715T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 112,049 control chromosomes in the GnomAD database, including 2 homozygotes. There are 59 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., 59 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: NDP NM_000266.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.792

Genes affected

NDP (HGNC:7678): (norrin cystine knot growth factor NDP) This gene encodes a secreted protein with a cystein-knot motif that activates the Wnt/beta-catenin pathway. The protein forms disulfide-linked oligomers in the extracellular matrix. Mutations in this gene result in Norrie disease and X-linked exudative vitreoretinopathy. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant X-43949084-A-G is Benign according to our data. Variant chrX-43949084-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 255688.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-43949084-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00162 (182/112049) while in subpopulation EAS AF= 0.0301 (107/3558). AF 95% confidence interval is 0.0255. There are 2 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDP	NM_000266.4	c.*715T>C		3_prime_UTR_variant	3/3	ENST00000642620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDP	ENST00000642620.1	c.*715T>C		3_prime_UTR_variant	3/3		NM_000266.4	P1
NDP	ENST00000647044.1	c.*715T>C		3_prime_UTR_variant	4/4			P1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 182 AN: 111999 Hom.: 2 Cov.: 23 AF XY: 0.00173 AC XY: 59 AN XY: 34173

Gnomad AFR AF: 0.0000974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00313

Gnomad ASJ AF: 0.00679

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.00444

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00132

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1355 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 253

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00162 AC: 182 AN: 112049 Hom.: 2 Cov.: 23 AF XY: 0.00172 AC XY: 59 AN XY: 34233

Gnomad4 AFR AF: 0.0000972

Gnomad4 AMR AF: 0.00312

Gnomad4 ASJ AF: 0.00679

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.00446

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.000516 Hom.: 15

Bravo AF: 0.00211

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	8.3
Dann	Benign	0.86

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: rs3747350; hg19: chrX-43808330;