chrX-70038122-G-C

Variant names:

• chrX-70038122-G-C
• rs3764746
• NM_001399.5:c.*2513G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399.5(EDA):​c.*2513G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 111,175 control chromosomes in the GnomAD database, including 518 homozygotes. There are 2,827 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 0.084 (518 hom., 2824 hem., cov: 22)
  • Exomes 𝑓: 0.094 (0 hom. 3 hem.)
• Consequence: EDA NM_001399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• 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, Orphanet, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286077 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.*2513G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.*2513G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001399.5	ENSP00000363680.4
EDA	ENST00000374553.6	c.*2513G>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000363681.2
ENSG00000286077	ENST00000651174.1	n.1045C>G		non_coding_transcript_exon_variant	Exon 2 of 2
EDA	ENST00000616899.1	c.*2513G>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000481963.1

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 9328 AN: 111089 Hom.: 506 Cov.: 22

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0378

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0907

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 1.00 AC: 1 AN: 1

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0455 AC: 1 AN: 22

Other (OTH) AF: 0.200 AC: 1 AN: 5

GnomAD4 genome AF: 0.0844 AC: 9376 AN: 111143 Hom.: 518 Cov.: 22 AF XY: 0.0846 AC XY: 2824 AN XY: 33387

African (AFR) AF: 0.136 AC: 4151 AN: 30502

American (AMR) AF: 0.207 AC: 2163 AN: 10456

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 51 AN: 2646

East Asian (EAS) AF: 0.182 AC: 627 AN: 3450

South Asian (SAS) AF: 0.216 AC: 559 AN: 2588

European-Finnish (FIN) AF: 0.0286 AC: 173 AN: 6043

Middle Eastern (MID) AF: 0.0461 AC: 10 AN: 217

European-Non Finnish (NFE) AF: 0.0259 AC: 1373 AN: 53053

Other (OTH) AF: 0.101 AC: 152 AN: 1508

Alfa AF: 0.0544 Hom.: 283

Bravo AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.54
PhyloP100		0.26
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: rs3764746; hg19: chrX-69257972;