rs876657687
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001399.5(EDA):c.960T>C(p.Tyr320Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,206,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000091 ( 0 hom., 1 hem., cov: 21)
Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )
Consequence
EDA
NM_001399.5 synonymous
NM_001399.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.527
Publications
1 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, 1Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- X-linked hypohidrotic ectodermal dysplasiaInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
- tooth agenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant X-70035393-T-C is Benign according to our data. Variant chrX-70035393-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2729786.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.527 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL,AD gene
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 | MANE Select | c.960T>C | p.Tyr320Tyr | synonymous | Exon 8 of 8 | NP_001390.1 | Q92838-1 | ||
| EDA | c.954T>C | p.Tyr318Tyr | synonymous | Exon 8 of 8 | NP_001005609.1 | Q92838-3 | |||
| EDA | c.951T>C | p.Tyr317Tyr | synonymous | Exon 8 of 8 | NP_001427690.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EDA | TSL:1 MANE Select | c.960T>C | p.Tyr320Tyr | synonymous | Exon 8 of 8 | ENSP00000363680.4 | Q92838-1 | ||
| EDA | TSL:1 | c.954T>C | p.Tyr318Tyr | synonymous | Exon 8 of 8 | ENSP00000363681.2 | Q92838-3 | ||
| EDA | TSL:1 | c.945T>C | p.Tyr315Tyr | synonymous | Exon 8 of 8 | ENSP00000432585.1 | Q92838-9 |
Frequencies
GnomAD3 genomes 0.00000908 AC: 1AN: 110103Hom.: 0 Cov.: 21 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
110103
Hom.:
Cov.:
21
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1096727Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 2AN XY: 362171 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1096727
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
362171
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
26381
American (AMR)
AF:
AC:
0
AN:
35082
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19338
East Asian (EAS)
AF:
AC:
0
AN:
30174
South Asian (SAS)
AF:
AC:
0
AN:
53815
European-Finnish (FIN)
AF:
AC:
0
AN:
40437
Middle Eastern (MID)
AF:
AC:
0
AN:
4132
European-Non Finnish (NFE)
AF:
AC:
2
AN:
841311
Other (OTH)
AF:
AC:
1
AN:
46057
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000908 AC: 1AN: 110103Hom.: 0 Cov.: 21 AF XY: 0.0000309 AC XY: 1AN XY: 32341 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
110103
Hom.:
Cov.:
21
AF XY:
AC XY:
1
AN XY:
32341
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30216
American (AMR)
AF:
AC:
0
AN:
10282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2626
East Asian (EAS)
AF:
AC:
0
AN:
3488
South Asian (SAS)
AF:
AC:
0
AN:
2493
European-Finnish (FIN)
AF:
AC:
0
AN:
5849
Middle Eastern (MID)
AF:
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
AC:
1
AN:
52755
Other (OTH)
AF:
AC:
0
AN:
1476
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Hypohidrotic X-linked ectodermal dysplasia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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