rs104894873

Variant names:

• chrX-43949817-G-A
• rs104894873
• NM_000266.4:c.384C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-43949817-G-A
• chrX-43949817-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000266.4(NDP):​c.384C>T​(p.Cys128Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,064,124 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000028 (0 hom. 2 hem.)
• Consequence: NDP NM_000266.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.256
• Publications: 4 publications found

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]

NDP-AS1 (HGNC:40395): (NDP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-43949817-G-A is Benign according to our data. Variant chrX-43949817-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2009980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.256 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000266.4. 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
	NDP	NM_000266.4	MANE Select	c.384C>T	p.Cys128Cys	synonymous	Exon 3 of 3	NP_000257.1	Q00604
	NDP-AS1	NR_046631.1		n.86G>A		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDP	ENST00000642620.1	MANE Select	c.384C>T	p.Cys128Cys	synonymous	Exon 3 of 3	ENSP00000495972.1	Q00604
	NDP	ENST00000647044.1		c.384C>T	p.Cys128Cys	synonymous	Exon 4 of 4	ENSP00000495811.1	Q00604
	NDP	ENST00000868527.1		c.384C>T	p.Cys128Cys	synonymous	Exon 3 of 3	ENSP00000538586.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000310 AC: 4 AN: 129186 AF XY: 0.0000479

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.000282

GnomAD4 exome AF: 0.00000282 AC: 3 AN: 1064124 Hom.: 0 Cov.: 30 AF XY: 0.00000577 AC XY: 2 AN XY: 346528

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25528

American (AMR) AF: 0.00 AC: 0 AN: 29554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18747

East Asian (EAS) AF: 0.00 AC: 0 AN: 28143

South Asian (SAS) AF: 0.0000397 AC: 2 AN: 50411

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 824349

Other (OTH) AF: 0.0000223 AC: 1 AN: 44856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.29
DANN	Benign	0.88
PhyloP100		-0.26
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs104894873; hg19: chrX-43809063;