dbSNP rs146017753: VMA21:p.Gly55Gly (chrX-151404917-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001017980.4(VMA21):c.165C>T(p.Gly55Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,203,457 control chromosomes in the GnomAD database, including 1 homozygotes. There are 703 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., 23 hem., cov: 22)

Exomes 𝑓: 0.0019 ( 1 hom. 680 hem. )

Consequence

VMA21
NM_001017980.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00004313

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00200

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant X-151404917-C-T is Benign according to our data. Variant chrX-151404917-C-T is described in ClinVar as Benign. ClinVar VariationId is 464818.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.002 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001017980.4 link	c.165C>T	p.Gly55Gly	splice_region_variant, synonymous_variant	Exon 3 of 3	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1 link	c.330C>T	p.Gly110Gly	splice_region_variant, synonymous_variant	Exon 3 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VMA21	ENST00000330374.7 link	c.165C>T	p.Gly55Gly	splice_region_variant, synonymous_variant	Exon 3 of 3	1	NM_001017980.4	ENSP00000333255.6	Q3ZAQ7-1
VMA21	ENST00000370361.5 link	c.330C>T	p.Gly110Gly	splice_region_variant, synonymous_variant	Exon 4 of 4	5		ENSP00000359386.1	Q3ZAQ7-2
VMA21	ENST00000477649.1 link	n.245C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.000949

AC:

102

AN:

107492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000602

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:

0.00163

Gnomad OTH

AF:

0.000694

GnomAD2 exomes

AF:

0.000966

AC:

175

AN:

181188

AF XY:

0.00109

show subpopulations

Gnomad AFR exome

AF:

0.000533

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.000404

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000128

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00186

AC:

2036

AN:

1095932

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

680

AN XY:

361618

show subpopulations

African (AFR)

AF:

0.000342

AC:

AN:

26354

American (AMR)

AF:

0.000171

AC:

AN:

35119

Ashkenazi Jewish (ASJ)

AF:

0.000207

AC:

AN:

19335

East Asian (EAS)

AF:

0.00

AC:

AN:

30174

South Asian (SAS)

AF:

0.0000374

AC:

AN:

53451

European-Finnish (FIN)

AF:

0.0000746

AC:

AN:

40201

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.00234

AC:

1967

AN:

841175

Other (OTH)

AF:

0.000978

AC:

AN:

46001

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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

AF:

0.000949

AC:

102

AN:

107525

Hom.:

Cov.:

AF XY:

0.000757

AC XY:

AN XY:

30391

show subpopulations

African (AFR)

AF:

0.000340

AC:

AN:

29383

American (AMR)

AF:

0.000601

AC:

AN:

9986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2611

East Asian (EAS)

AF:

0.00

AC:

AN:

3429

South Asian (SAS)

AF:

0.00

AC:

AN:

2420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5105

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00163

AC:

AN:

52240

Other (OTH)

AF:

0.000686

AC:

AN:

1457

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00137

Hom.:

Bravo

AF:

0.000979

EpiCase

AF:

0.00191

EpiControl

AF:

0.00137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked myopathy with excessive autophagy

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.42

CADD

Benign

0.87

(source)

DANN

Benign

0.61

PhyloP100

0.0020

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=80/20

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000043

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over