X-151404910-T-G

Variant names:

• chrX-151404910-T-G
• rs878854356
• NM_001017980.4:c.164-6T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001017980.4(VMA21):​c.164-6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: VMA21 NM_001017980.4 splice_region, intron
• Scores: Splicing: ADA: 0.002313
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.761

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-151404910-T-G is Pathogenic according to our data. Variant chrX-151404910-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 208804.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-151404910-T-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001017980.4	c.164-6T>G		splice_region_variant, intron_variant	Intron 2 of 2	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1	c.329-6T>G		splice_region_variant, intron_variant	Intron 2 of 2		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7	c.164-6T>G		splice_region_variant, intron_variant	Intron 2 of 2	1	NM_001017980.4	ENSP00000333255.6
VMA21	ENST00000370361.5	c.329-6T>G		splice_region_variant, intron_variant	Intron 3 of 3	5		ENSP00000359386.1
VMA21	ENST00000477649.1	n.244-6T>G		splice_region_variant, intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

X-linked myopathy with excessive autophagy Pathogenic:1

Apr 21, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	8.1
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0023
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.49		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs878854356; hg19: chrX-150573382;