rs5936487

Variant names:

• chrX-69673072-G-A
• rs5936487
• NM_001399.5:c.396+56368G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-69673072-G-A
• chrX-69673072-G-C
• chrX-69673072-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001399.5(EDA):​c.396+56368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.66 (17624 hom., 20881 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.396+56368G>A		intron_variant	Intron 1 of 7	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.396+56368G>A		intron_variant	Intron 1 of 7	1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 72092 AN: 109613 Hom.: 17619 Cov.: 22

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.628

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.658 AC: 72148 AN: 109663 Hom.: 17624 Cov.: 22 AF XY: 0.654 AC XY: 20881 AN XY: 31907

African (AFR) AF: 0.808 AC: 24379 AN: 30162

American (AMR) AF: 0.710 AC: 7273 AN: 10241

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1346 AN: 2619

East Asian (EAS) AF: 0.997 AC: 3482 AN: 3493

South Asian (SAS) AF: 0.721 AC: 1808 AN: 2509

European-Finnish (FIN) AF: 0.594 AC: 3353 AN: 5644

Middle Eastern (MID) AF: 0.424 AC: 92 AN: 217

European-Non Finnish (NFE) AF: 0.551 AC: 29002 AN: 52607

Other (OTH) AF: 0.633 AC: 949 AN: 1500

Alfa AF: 0.588 Hom.: 88216

Bravo AF: 0.677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.93
DANN	Benign	0.81
PhyloP100		-0.62
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: rs5936487; hg19: chrX-68892916;