rs10579679

Variant names:

• chrX-70028046-CCT-C
• rs10579679
• NM_001399.5:c.706+11_706+12delCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001399.5(EDA):​c.706+11_706+12delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,193,389 control chromosomes in the GnomAD database, including 71,235 homozygotes. There are 154,984 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (8117 hom., 13038 hem., cov: 0)
  • Exomes 𝑓: 0.41 (63118 hom. 141946 hem.)
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.988
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-70028046-CCT-C is Benign according to our data. Variant chrX-70028046-CCT-C is described in ClinVar as Benign. ClinVar VariationId is 44204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

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.706+11_706+12delCT		intron	N/A	NP_001390.1	Q92838-1
	EDA	NM_001005609.2		c.706+11_706+12delCT		intron	N/A	NP_001005609.1	Q92838-3
	EDA	NM_001440761.1		c.706+11_706+12delCT		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.706+11_706+12delCT		intron	N/A	ENSP00000363680.4	Q92838-1
	EDA	ENST00000374553.6	TSL:1	c.706+11_706+12delCT		intron	N/A	ENSP00000363681.2	Q92838-3
	EDA	ENST00000524573.5	TSL:1	c.706+11_706+12delCT		intron	N/A	ENSP00000432585.1	Q92838-9

Frequencies

GnomAD3 genomes AF: 0.442 AC: 47876 AN: 108293 Hom.: 8118 Cov.: 0

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.404

GnomAD2 exomes AF: 0.371 AC: 57799 AN: 155702 AF XY: 0.356

Gnomad AFR exome AF: 0.581

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.406 AC: 440908 AN: 1085050 Hom.: 63118 AF XY: 0.401 AC XY: 141946 AN XY: 354172

African (AFR) AF: 0.588 AC: 15244 AN: 25928

American (AMR) AF: 0.310 AC: 10558 AN: 34104

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 5736 AN: 19115

East Asian (EAS) AF: 0.154 AC: 4537 AN: 29488

South Asian (SAS) AF: 0.276 AC: 14431 AN: 52202

European-Finnish (FIN) AF: 0.483 AC: 19171 AN: 39727

Middle Eastern (MID) AF: 0.394 AC: 1247 AN: 3162

European-Non Finnish (NFE) AF: 0.421 AC: 351872 AN: 835856

Other (OTH) AF: 0.398 AC: 18112 AN: 45468

GnomAD4 genome AF: 0.442 AC: 47906 AN: 108339 Hom.: 8117 Cov.: 0 AF XY: 0.423 AC XY: 13038 AN XY: 30815

African (AFR) AF: 0.576 AC: 17027 AN: 29568

American (AMR) AF: 0.352 AC: 3620 AN: 10270

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 740 AN: 2613

East Asian (EAS) AF: 0.176 AC: 602 AN: 3420

South Asian (SAS) AF: 0.249 AC: 612 AN: 2455

European-Finnish (FIN) AF: 0.491 AC: 2709 AN: 5514

Middle Eastern (MID) AF: 0.371 AC: 78 AN: 210

European-Non Finnish (NFE) AF: 0.415 AC: 21652 AN: 52139

Other (OTH) AF: 0.408 AC: 608 AN: 1489

Alfa AF: 0.421 Hom.: 4262

Bravo AF: 0.444

Asia WGS AF: 0.248 AC: 628 AN: 2522

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Hypohidrotic X-linked ectodermal dysplasia (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99
Mutation Taster		=90/10	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10579679; hg19: chrX-69247896;