X-69666995-A-T

Variant names:

• chrX-69666995-A-T
• rs4844185
• NM_001399.5:c.396+50291A>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+50291A>T 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 0.0 (0 hom., 0 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399.5. 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
	EDA	NM_001399.5	MANE Select	c.396+50291A>T		intron	N/A	NP_001390.1	Q92838-1
	EDA	NM_001005609.2		c.396+50291A>T		intron	N/A	NP_001005609.1	Q92838-3
	EDA	NM_001440761.1		c.396+50291A>T		intron	N/A	NP_001427690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA	ENST00000374552.9	TSL:1 MANE Select	c.396+50291A>T		intron	N/A	ENSP00000363680.4	Q92838-1
	EDA	ENST00000374553.6	TSL:1	c.396+50291A>T		intron	N/A	ENSP00000363681.2	Q92838-3
	EDA	ENST00000524573.5	TSL:1	c.396+50291A>T		intron	N/A	ENSP00000432585.1	Q92838-9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 109283 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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: AC0 AF: 0.00 AC: 0 AN: 109283 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 31675

African (AFR) AF: 0.00 AC: 0 AN: 30203

American (AMR) AF: 0.00 AC: 0 AN: 10239

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.00 AC: 0 AN: 3540

South Asian (SAS) AF: 0.00 AC: 0 AN: 2585

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 221

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52402

Other (OTH) AF: 0.00 AC: 0 AN: 1475

Alfa AF: 0.00 Hom.: 1604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.27
PhyloP100		0.072

Splicing

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

Other links and lift over

dbSNP: rs4844185; hg19: chrX-68886839;