Genetic Variant VMA21:c.218+31G>T (chrX-151397088-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363810.1(VMA21):c.218+31G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 13647 hom., 18281 hem., cov: 22)

Exomes 𝑓: 0.52 ( 30628 hom. 56665 hem. )

Failed GnomAD Quality Control

Consequence

VMA21
NM_001363810.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.68

Variant links:

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 links:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-151397088-G-T is Benign according to our data. Variant chrX-151397088-G-T is described in ClinVar as [Benign]. Clinvar id is 1283501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1 link	c.218+31G>T		intron_variant	Intron 1 of 2		NP_001350739.1
VMA21	NM_001017980.4 link	c.-221G>T		upstream_gene_variant		ENST00000330374.7	NP_001017980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7 link	c.-221G>T		upstream_gene_variant		1	NM_001017980.4	ENSP00000333255.6		Q3ZAQ7-1

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

62881

AN:

109605

Hom.:

13638

Cov.:

AF XY:

0.561

AC XY:

18259

AN XY:

32571

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.483

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.530

GnomAD3 exomes

AF:

0.484

AC:

18580

AN:

38363

Hom.:

4253

AF XY:

0.547

AC XY:

2588

AN XY:

4733

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.581

Gnomad NFE exome

AF:

0.577

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.517

AC:

170712

AN:

330499

Hom.:

30628

Cov.:

AF XY:

0.537

AC XY:

56665

AN XY:

105563

show subpopulations

Gnomad4 AFR exome

AF:

0.771

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.574

AC:

62909

AN:

109638

Hom.:

13647

Cov.:

AF XY:

0.561

AC XY:

18281

AN XY:

32614

show subpopulations

Gnomad4 AFR

AF:

0.753

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.500

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.559

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.437

Hom.:

3490

Bravo

AF:

0.562

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.035

DANN

Benign

0.31

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over