X-69616689-C-A

Variant names:

• chrX-69616689-C-A
• NM_001399.5:c.381C>A
• EDA p.Ser127Ser

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001399.5(EDA):​c.381C>A​(p.Ser127Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S127S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: EDA NM_001399.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

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.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	NP_001390.1	Q92838-1
	EDA	NM_001005609.2		c.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	NP_001005609.1	Q92838-3
	EDA	NM_001440761.1		c.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	NP_001427690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDA	ENST00000374552.9	TSL:1 MANE Select	c.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	ENSP00000363680.4	Q92838-1
	EDA	ENST00000374553.6	TSL:1	c.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	ENSP00000363681.2	Q92838-3
	EDA	ENST00000524573.5	TSL:1	c.381C>A	p.Ser127Ser	synonymous	Exon 1 of 8	ENSP00000432585.1	Q92838-9

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.45

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-68836533;