rs182251004

Variant names:

• chrX-69616609-C-G
• NM_001399.5:c.301C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-69616609-C-G
• chrX-69616609-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001399.5(EDA):​c.301C>G​(p.Pro101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,143 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: EDA NM_001399.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31505924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.301C>G	p.Pro101Ala	missense_variant	Exon 1 of 8	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.301C>G	p.Pro101Ala	missense_variant	Exon 1 of 8	1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098143 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363573

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	9.6
DANN	Benign	0.94
DEOGEN2	Benign	0.38	.;.;.;.;T;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	0.81	L;L;L;L;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.2	D;D;D;N;N;N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D;D;D;.;.
Sift4G	Benign	0.081	T;T;T;T;T;T
Polyphen		0.78	P;P;P;B;B;B
Vest4		0.19
MutPred		0.39		Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.95
MPC		0.76
ClinPred		0.21	T
GERP RS		1.4
Varity_R		0.29
gMVP		0.68

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-68836453;