rs1556035617

Variant names:

• chrX-151405070-CCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG-C
• rs1556035617
• NM_001017980.4:c.*13_*104delCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_001017980.4(VMA21):​c.*13_*104delCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: VMA21 NM_001017980.4 3_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.22
• Publications: 6 publications found

Genes affected

VMA21 (HGNC:22082): (vacuolar ATPase assembly factor VMA21) This gene encodes a chaperone for assembly of lysosomal vacuolar ATPase.[provided by RefSeq, Jul 2012]

VMA21 Gene-Disease associations (from GenCC):

• X-linked myopathy with excessive autophagy

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP5: Variant X-151405070-CCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG-C is Pathogenic according to our data. Variant chrX-151405070-CCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 208805.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001017980.4	c.*13_*104delCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG		3_prime_UTR_variant	Exon 3 of 3	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1	c.*13_*104delCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG		3_prime_UTR_variant	Exon 3 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7	c.*13_*104delCTTTTTATAGCATTAAATTCATTTTTTAAAATGATAAATGCTGGAGGGGGCCATCTGATTTGAATAAAGTTGAAAGAACATGTTAAAGTCAG		3_prime_UTR_variant	Exon 3 of 3	1	NM_001017980.4	ENSP00000333255.6

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

X-linked myopathy with excessive autophagy Pathogenic:1

Mar 01, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=30/70	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1556035617; hg19: chrX-150573542;