Variant rs61747506 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM5BP4_ModerateBP6_ModerateBS2

The NM_001399.5(EDA):c.1070G>A(p.Arg357Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,206,739 control chromosomes in the GnomAD database, including 1 homozygotes. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000051 ( 1 hom. 17 hem. )

Consequence

EDA
NM_001399.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.94

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

BP4

Computational evidence support a benign effect (MetaRNN=0.15601006).

BP6

Variant X-70035503-G-A is Benign according to our data. Variant chrX-70035503-G-A is described in ClinVar as [Benign]. Clinvar id is 528362.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA	NM_001399.5 linkuse as main transcript	c.1070G>A	p.Arg357Gln	missense_variant	8/8	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9 linkuse as main transcript	c.1070G>A	p.Arg357Gln	missense_variant	8/8	1	NM_001399.5	ENSP00000363680	P4	Q92838-1
EDA	ENST00000374553.6 linkuse as main transcript	c.1064G>A	p.Arg355Gln	missense_variant	8/8	1		ENSP00000363681	A1	Q92838-3
EDA	ENST00000524573.5 linkuse as main transcript	c.1055G>A	p.Arg352Gln	missense_variant	8/8	1		ENSP00000432585	A1	Q92838-9
EDA	ENST00000616899.1 linkuse as main transcript	c.674G>A	p.Arg225Gln	missense_variant	7/7	5		ENSP00000481963

Frequencies

GnomAD3 genomes

AF:

0.0000553

AC:

AN:

108523

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

30881

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00154

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000191

Gnomad OTH

AF:

0.000693

GnomAD3 exomes

AF:

0.0000766

AC:

AN:

182702

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

67454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1098216

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

363570

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00175

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000166

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000553

AC:

AN:

108523

Hom.:

Cov.:

AF XY:

0.0000324

AC XY:

AN XY:

30881

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00154

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.000693

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypohidrotic X-linked ectodermal dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

.;D;.;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Pathogenic

0.90

MutationAssessor

Benign

0.69

.;N;.;.

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.56

N;N;N;.

REVEL

Uncertain

0.54

Sift

Benign

0.038

D;.;.;.

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.73

P;P;P;.

Vest4

0.31

MVP

0.98

MPC

1.1

ClinPred

0.18

GERP RS

4.5

Varity_R

0.79

gMVP

0.78

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over