X-151396858-G-C

Variant names:

• chrX-151396858-G-C
• rs176451
• NM_001363810.1:c.19G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363810.1(VMA21):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (13688 hom., 17503 hem., cov: 21)
  • Exomes 𝑓: 0.50 (34664 hom. 75315 hem.)
  • Failed GnomAD Quality Control
• Consequence: VMA21 NM_001363810.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.736
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4144747E-5).
• BP6: Variant X-151396858-G-C is Benign according to our data. Variant chrX-151396858-G-C is described in ClinVar as Benign. ClinVar VariationId is 1684210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363810.1. 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_001363810.1		c.19G>C	p.Gly7Arg	missense	Exon 1 of 3	NP_001350739.1	Q3ZAQ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA21	ENST00000370361.5	TSL:5	c.19G>C	p.Gly7Arg	missense	Exon 2 of 4	ENSP00000359386.1	Q3ZAQ7-2
	ENSG00000287918	ENST00000660681.3		n.280C>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000287918	ENST00000664935.1		n.161C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 62315 AN: 109233 Hom.: 13679 Cov.: 21

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.526

GnomAD2 exomes AF: 0.461 AC: 46235 AN: 100226 AF XY: 0.460

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.309

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.173

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.502 AC: 205927 AN: 409878 Hom.: 34664 Cov.: 0 AF XY: 0.500 AC XY: 75315 AN XY: 150492

African (AFR) AF: 0.762 AC: 9423 AN: 12374

American (AMR) AF: 0.319 AC: 8545 AN: 26752

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 7157 AN: 14595

East Asian (EAS) AF: 0.192 AC: 4611 AN: 24055

South Asian (SAS) AF: 0.439 AC: 16590 AN: 37749

European-Finnish (FIN) AF: 0.553 AC: 19822 AN: 35876

Middle Eastern (MID) AF: 0.545 AC: 1619 AN: 2970

European-Non Finnish (NFE) AF: 0.544 AC: 126398 AN: 232430

Other (OTH) AF: 0.510 AC: 11762 AN: 23077

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.571 AC: 62355 AN: 109278 Hom.: 13688 Cov.: 21 AF XY: 0.553 AC XY: 17503 AN XY: 31676

African (AFR) AF: 0.753 AC: 22556 AN: 29969

American (AMR) AF: 0.380 AC: 3988 AN: 10495

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1304 AN: 2627

East Asian (EAS) AF: 0.172 AC: 590 AN: 3422

South Asian (SAS) AF: 0.409 AC: 996 AN: 2438

European-Finnish (FIN) AF: 0.544 AC: 3045 AN: 5598

Middle Eastern (MID) AF: 0.469 AC: 100 AN: 213

European-Non Finnish (NFE) AF: 0.547 AC: 28663 AN: 52363

Other (OTH) AF: 0.528 AC: 788 AN: 1492

Alfa AF: 0.432 Hom.: 3356

Bravo AF: 0.561

TwinsUK AF: 0.538 AC: 1994

ALSPAC AF: 0.541 AC: 1564

ExAC AF: 0.456 AC: 7873

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	X-linked myopathy with excessive autophagy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.94	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.66
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.74
PROVEAN	Benign	0.18	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Vest4		0.032
ClinPred		0.0059	T
GERP RS		-2.6
PromoterAI		-0.043	Neutral
gMVP		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs176451; hg19: chrX-150565330; COSMIC: COSV57756648; COSMIC: COSV57756648;