dbSNP rs176452: VMA21:c.218+31G>T (chrX-151397088-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

X-linked myopathy with excessive autophagy
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

VMA21 links:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.218+31G>T		intron	N/A	NP_001350739.1	Q3ZAQ7-2
	VMA21	NM_001017980.4	MANE Select	c.-221G>T		upstream_gene	N/A	NP_001017980.1	Q3ZAQ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VMA21	ENST00000370361.5	TSL:5	c.218+31G>T	intron	N/A	ENSP00000359386.1	Q3ZAQ7-2
ENSG00000287918	ENST00000660681.3		n.50C>A	non_coding_transcript_exon	Exon 1 of 2
ENSG00000287918	ENST00000668689.1		n.55C>A	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

62881

AN:

109605

Hom.:

13638

Cov.:

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

GnomAD2 exomes

AF:

0.484

AC:

18580

AN:

38363

AF XY:

0.547

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 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

African (AFR)

AF:

0.771

AC:

7046

AN:

9135

American (AMR)

AF:

0.331

AC:

5455

AN:

16503

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

5284

AN:

10451

East Asian (EAS)

AF:

0.199

AC:

4246

AN:

21288

South Asian (SAS)

AF:

0.470

AC:

12455

AN:

26482

European-Finnish (FIN)

AF:

0.560

AC:

13056

AN:

23300

Middle Eastern (MID)

AF:

0.524

AC:

750

AN:

1431

European-Non Finnish (NFE)

AF:

0.555

AC:

112287

AN:

202391

Other (OTH)

AF:

0.519

AC:

10133

AN:

19518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

2246

4492

6738

8984

11230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.753

AC:

22863

AN:

30353

American (AMR)

AF:

0.381

AC:

4032

AN:

10570

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1305

AN:

2611

East Asian (EAS)

AF:

0.182

AC:

591

AN:

3254

South Asian (SAS)

AF:

0.416

AC:

1096

AN:

2636

European-Finnish (FIN)

AF:

0.559

AC:

3071

AN:

5489

Middle Eastern (MID)

AF:

0.472

AC:

101

AN:

214

European-Non Finnish (NFE)

AF:

0.549

AC:

28725

AN:

52352

Other (OTH)

AF:

0.532

AC:

799

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

872

1744

2616

3488

4360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.437

Hom.:

3490

Bravo

AF:

0.562

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.035

(source)

DANN

Benign

0.31

PhyloP100

-2.7

PromoterAI

-0.084

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over