chrX-151397337-A-G

Variant names:

• chrX-151397337-A-G
• rs1197341312
• NM_001017980.4:c.29A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017980.4(VMA21):​c.29A>G​(p.Asn10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,161,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: VMA21 NM_001017980.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000287918 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10524058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017980.4. 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
	VMA21	NM_001017980.4	MANE Select	c.29A>G	p.Asn10Ser	missense	Exon 1 of 3	NP_001017980.1	Q3ZAQ7-1
	VMA21	NM_001363810.1		c.218+280A>G		intron	N/A	NP_001350739.1	Q3ZAQ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA21	ENST00000330374.7	TSL:1 MANE Select	c.29A>G	p.Asn10Ser	missense	Exon 1 of 3	ENSP00000333255.6	Q3ZAQ7-1
	VMA21	ENST00000932111.1		c.29A>G	p.Asn10Ser	missense	Exon 1 of 3	ENSP00000602170.1
	VMA21	ENST00000370361.5	TSL:5	c.218+280A>G		intron	N/A	ENSP00000359386.1	Q3ZAQ7-2

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113236 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1048463 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 342415

African (AFR) AF: 0.00 AC: 0 AN: 24910

American (AMR) AF: 0.00 AC: 0 AN: 27945

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18636

East Asian (EAS) AF: 0.00 AC: 0 AN: 27131

South Asian (SAS) AF: 0.00 AC: 0 AN: 49820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32461

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4016

European-Non Finnish (NFE) AF: 0.00000244 AC: 2 AN: 819258

Other (OTH) AF: 0.00 AC: 0 AN: 44286

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113236 Hom.: 0 Cov.: 24 AF XY: 0.0000283 AC XY: 1 AN XY: 35396

African (AFR) AF: 0.00 AC: 0 AN: 31265

American (AMR) AF: 0.00 AC: 0 AN: 10880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53296

Other (OTH) AF: 0.00 AC: 0 AN: 1530

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	X-linked myopathy with excessive autophagy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.0021	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.056
Sift	Benign	0.25	T
Sift4G	Benign	0.70	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.21		Gain of glycosylation at N10 (P = 0.0466)
MVP		0.12
MPC		0.63
ClinPred		0.18	T
GERP RS		3.8
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1197341312; hg19: chrX-150565809;