X-151397335-G-C

Variant names:

• chrX-151397335-G-C
• rs2011201339
• NM_001017980.4:c.27G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001017980.4(VMA21):​c.27G>C​(p.Leu9Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000763 in 1,048,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000076 (0 hom. 3 hem.)
• Consequence: VMA21 NM_001017980.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant X-151397335-G-C is Benign according to our data. Variant chrX-151397335-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2902618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

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.27G>C	p.Leu9Leu	synonymous	Exon 1 of 3	NP_001017980.1	Q3ZAQ7-1
	VMA21	NM_001363810.1		c.218+278G>C		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.27G>C	p.Leu9Leu	synonymous	Exon 1 of 3	ENSP00000333255.6	Q3ZAQ7-1
	VMA21	ENST00000932111.1		c.27G>C	p.Leu9Leu	synonymous	Exon 1 of 3	ENSP00000602170.1
	VMA21	ENST00000370361.5	TSL:5	c.218+278G>C		intron	N/A	ENSP00000359386.1	Q3ZAQ7-2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000763 AC: 8 AN: 1048508 Hom.: 0 Cov.: 30 AF XY: 0.00000876 AC XY: 3 AN XY: 342492

African (AFR) AF: 0.00 AC: 0 AN: 24912

American (AMR) AF: 0.00 AC: 0 AN: 27949

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18646

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 49782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32451

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4014

European-Non Finnish (NFE) AF: 0.00000976 AC: 8 AN: 819327

Other (OTH) AF: 0.00 AC: 0 AN: 44296

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		1.2
PromoterAI		-0.0021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2011201339; hg19: chrX-150565807;