X-70038665-T-G

Position:

• chrX-70038665-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399.5(EDA):​c.*3056T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 111,085 control chromosomes in the GnomAD database, including 4,767 homozygotes. There are 10,912 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 0.33 (4750 hom., 10851 hem., cov: 22)
  • Exomes 𝑓: 0.48 (17 hom. 61 hem.)
• Consequence: EDA NM_001399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDA	NM_001399.5	c.*3056T>G		3_prime_UTR_variant	8/8	ENST00000374552.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDA	ENST00000374552.9	c.*3056T>G		3_prime_UTR_variant	8/8	1	NM_001399.5	P4
EDA	ENST00000374553.6	c.*3056T>G		3_prime_UTR_variant	8/8	1		A1
	ENST00000651174.1	n.502A>C		non_coding_transcript_exon_variant	2/2
EDA	ENST00000616899.1	c.*3056T>G		3_prime_UTR_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.328 AC: 36354 AN: 110718 Hom.: 4738 Cov.: 22 AF XY: 0.328 AC XY: 10817 AN XY: 32942

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.477 AC: 147 AN: 308 Hom.: 17 Cov.: 0 AF XY: 0.455 AC XY: 61 AN XY: 134

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.329 AC: 36398 AN: 110777 Hom.: 4750 Cov.: 22 AF XY: 0.329 AC XY: 10851 AN XY: 33011

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.361

Alfa AF: 0.352 Hom.: 15181

Bravo AF: 0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795170; hg19: chrX-69258515; COSMIC: COSV52143414; COSMIC: COSV52143414;