chrX-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. 10/13 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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.19G>C	p.Gly7Arg	missense_variant	Exon 1 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000370361.5	c.19G>C	p.Gly7Arg	missense_variant	Exon 2 of 4	5		ENSP00000359386.1
ENSG00000287918	ENST00000660681.2	n.280C>G		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1	n.161C>G		non_coding_transcript_exon_variant	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

Gnomad4 AFR exome AF: 0.762 AC: 9423 AN: 12374

Gnomad4 AMR exome AF: 0.319 AC: 8545 AN: 26752

Gnomad4 ASJ exome AF: 0.490 AC: 7157 AN: 14595

Gnomad4 EAS exome AF: 0.192 AC: 4611 AN: 24055

Gnomad4 SAS exome AF: 0.439 AC: 16590 AN: 37749

Gnomad4 FIN exome AF: 0.553 AC: 19822 AN: 35876

Gnomad4 NFE exome AF: 0.544 AC: 126398 AN: 232430

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.753 AC: 0.752644 AN: 0.752644

Gnomad4 AMR AF: 0.380 AC: 0.37999 AN: 0.37999

Gnomad4 ASJ AF: 0.496 AC: 0.496384 AN: 0.496384

Gnomad4 EAS AF: 0.172 AC: 0.172414 AN: 0.172414

Gnomad4 SAS AF: 0.409 AC: 0.408532 AN: 0.408532

Gnomad4 FIN AF: 0.544 AC: 0.543944 AN: 0.543944

Gnomad4 NFE AF: 0.547 AC: 0.54739 AN: 0.54739

Gnomad4 OTH AF: 0.528 AC: 0.52815 AN: 0.52815

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

X-linked myopathy with excessive autophagy Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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
gMVP		0.053
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

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