Variant rs146017753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001017980.4(VMA21):c.165C>T(p.Gly55=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
VMA21	NM_001017980.4 linkuse as main transcript	c.165C>T	p.Gly55=	splice_region_variant, synonymous_variant	3/3	ENST00000330374.7
VMA21	NM_001363810.1 linkuse as main transcript	c.330C>T	p.Gly110=	splice_region_variant, synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VMA21	ENST00000330374.7 linkuse as main transcript	c.165C>T	p.Gly55=	splice_region_variant, synonymous_variant	3/3	1	NM_001017980.4	P1	Q3ZAQ7-1
VMA21	ENST00000370361.5 linkuse as main transcript	c.330C>T	p.Gly110=	splice_region_variant, synonymous_variant	4/4	5			Q3ZAQ7-2
VMA21	ENST00000477649.1 linkuse as main transcript	n.245C>T		splice_region_variant, non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000949

AC:

102

AN:

107492

Hom.:

Cov.:

AF XY:

0.000758

AC XY:

AN XY:

30348

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

GnomAD3 exomes

AF:

0.000966

AC:

175

AN:

181188

Hom.:

AF XY:

0.00109

AC XY:

AN XY:

65898

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 SAS 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

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.000207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000374

Gnomad4 FIN exome

AF:

0.0000746

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.000978

GnomAD4 genome

AF:

0.000949

AC:

102

AN:

107525

Hom.:

Cov.:

AF XY:

0.000757

AC XY:

AN XY:

30391

show subpopulations

Gnomad4 AFR

AF:

0.000340

Gnomad4 AMR

AF:

0.000601

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.000686

Alfa

AF:

0.00149

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.87

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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