NM_001399.5:c.502+4530T>C

Variant names:

• chrX-69961662-T-C
• rs10521347
• NM_001399.5:c.502+4530T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399.5(EDA):​c.502+4530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 112,131 control chromosomes in the GnomAD database, including 935 homozygotes. There are 3,634 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: 𝑓 0.10 (935 hom., 3634 hem., cov: 23)
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 0 publications found

Genes affected

EDA (HGNC:3157): (ectodysplasin A) The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

EDA Gene-Disease associations (from GenCC):

• tooth agenesis, selective, X-linked, 1

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• X-linked hypohidrotic ectodermal dysplasia

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.502+4530T>C		intron_variant	Intron 2 of 7	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.502+4530T>C		intron_variant	Intron 2 of 7	1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 11255 AN: 112077 Hom.: 931 Cov.: 23

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.0350

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.0468

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 11288 AN: 112131 Hom.: 935 Cov.: 23 AF XY: 0.106 AC XY: 3634 AN XY: 34323

African (AFR) AF: 0.0968 AC: 2997 AN: 30955

American (AMR) AF: 0.256 AC: 2705 AN: 10557

Ashkenazi Jewish (ASJ) AF: 0.0350 AC: 93 AN: 2656

East Asian (EAS) AF: 0.611 AC: 2140 AN: 3501

South Asian (SAS) AF: 0.239 AC: 638 AN: 2673

European-Finnish (FIN) AF: 0.0717 AC: 438 AN: 6108

Middle Eastern (MID) AF: 0.0467 AC: 10 AN: 214

European-Non Finnish (NFE) AF: 0.0365 AC: 1942 AN: 53258

Other (OTH) AF: 0.113 AC: 174 AN: 1534

Alfa AF: 0.103 Hom.: 2186

Bravo AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.48
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10521347; hg19: chrX-69181512;