X-151396890-G-C

Variant names:

• chrX-151396890-G-C
• rs138128701
• NM_001363810.1:c.51G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001363810.1(VMA21):​c.51G>C​(p.Glu17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 522,449 control chromosomes in the GnomAD database, including 4 homozygotes. There are 119 hemizygotes in GnomAD. 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., 79 hem., cov: 21)
  • Exomes 𝑓: 0.00043 (1 hom. 40 hem.)
• Consequence: VMA21 NM_001363810.1 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0860

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035504699).
• BP6: Variant X-151396890-G-C is Benign according to our data. Variant chrX-151396890-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1690444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.51G>C	p.Glu17Asp	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.51G>C	p.Glu17Asp	missense_variant	Exon 2 of 4	5		ENSP00000359386.1
ENSG00000287918	ENST00000660681.2	n.248C>G		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1	n.129C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 283 AN: 110576 Hom.: 3 Cov.: 21

Gnomad AFR AF: 0.00873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

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: 0.0000379

Gnomad OTH AF: 0.00135

GnomAD2 exomes AF: 0.000507 AC: 52 AN: 102574 AF XY: 0.000348

Gnomad AFR exome AF: 0.00842

Gnomad AMR exome AF: 0.000471

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000435 AC: 179 AN: 411828 Hom.: 1 Cov.: 0 AF XY: 0.000263 AC XY: 40 AN XY: 151894

Gnomad4 AFR exome AF: 0.0103 AC: 129 AN: 12487

Gnomad4 AMR exome AF: 0.000444 AC: 12 AN: 27057

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 14653

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 24102

Gnomad4 SAS exome AF: 0.0000792 AC: 3 AN: 37863

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 36056

Gnomad4 NFE exome AF: 0.0000428 AC: 10 AN: 233453

Gnomad4 Remaining exome AF: 0.000733 AC: 17 AN: 23178

GnomAD4 genome AF: 0.00259 AC: 286 AN: 110621 Hom.: 3 Cov.: 21 AF XY: 0.00240 AC XY: 79 AN XY: 32859

Gnomad4 AFR AF: 0.00881 AC: 0.00880739 AN: 0.00880739

Gnomad4 AMR AF: 0.00132 AC: 0.0013225 AN: 0.0013225

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000379 AC: 0.0000379341 AN: 0.0000379341

Gnomad4 OTH AF: 0.00133 AC: 0.00133156 AN: 0.00133156

Alfa AF: 0.00221 Hom.: 5

Bravo AF: 0.00265

ExAC AF: 0.000163 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

See cases Benign:1

Sep 01, 2021

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG classification criteria: BS2, BP4 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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	-0.80	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.69
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.028
Sift	Pathogenic	0.0	D
Vest4		0.057
MutPred		0.085		Loss of helix (P = 0.079);
MVP		0.29
ClinPred		0.0063	T
GERP RS		-0.85
gMVP		0.072
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138128701; hg19: chrX-150565362;