rs713993050

chrX-153725514-T-TC

• Frequency: Genomes: not found (cov: 25)
• Consequence: ABCD1 NM_000033 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 1.13

ACMG classification

Verdict is Pathogenic. Variant got 17 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. There are 342 pathogenic variants in the truncated region.
• PM2: Very rare variant; Number of alleles below threshold, Median coverage is 25.
• PP5: Variant X:153725514-T>TC is Pathogenic according to our data. Variant chrX-153725514-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 162148. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD1	NM_000033.4	c.253dup	p.Arg85ProfsTer110	frameshift_variant	1/10	ENST00000218104.6
ABCD1	XM_047441916.1	c.253dup	p.Arg85ProfsTer110	frameshift_variant	1/11
ABCD1	XM_047441917.1	c.253dup	p.Arg85ProfsTer110	frameshift_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD1	ENST00000218104.6	c.253dup	p.Arg85ProfsTer110	frameshift_variant	1/10	1	NM_000033.4	P1

Frequencies

GnomAD3 genomes Cov.: 25

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

LINK:

Submissions by phenotype

Adrenoleukodystrophy Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Invitae	May 05, 2022	This sequence change creates a premature translational stop signal (p.Arg85Profs*110) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of X-linked adrenoleukodystrophy (PMID: 15811009, 27489563). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162148). For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, no assertion criteria provided	research	Faculty of Medicine, Iran University of Medical Sciences (IUMS)	Sep 17, 2014	Present study is the first to report clinical and genetics characteristics of Iranian X-ALD patients, Lorestan province. It also highlighted the importance of genetic counseling through reliable identification of heterozygous as well as homozygote females in consanguineous communities with subsequent elevated prevalence. Unexpectedly, there exist childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease phenotypes of ALD in our pedigree with the same variant. X-ALD also occurred significantly more in our studied Iranian pedigree compared to its reported prevalence (Odd Ratio 4249.7500, 95% CI 224.6575 to 80390.7075, p-value< 0.0001). -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 02, 2015

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs713993050; hg19: chrX-152990969;