X-151397317-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001017980.4(VMA21):​c.9C>T​(p.Arg3Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000603 in 1,160,992 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.0000038 ( 0 hom. 2 hem. )

Consequence

VMA21
NM_001017980.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0400
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant X-151397317-C-T is Benign according to our data. Variant chrX-151397317-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2729321.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.04 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VMA21NM_001017980.4 linkc.9C>T p.Arg3Arg synonymous_variant Exon 1 of 3 ENST00000330374.7 NP_001017980.1
VMA21NM_001363810.1 linkc.218+260C>T intron_variant Intron 1 of 2 NP_001350739.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VMA21ENST00000330374.7 linkc.9C>T p.Arg3Arg synonymous_variant Exon 1 of 3 1 NM_001017980.4 ENSP00000333255.6 Q3ZAQ7-1
VMA21ENST00000370361.5 linkc.218+260C>T intron_variant Intron 2 of 3 5 ENSP00000359386.1 Q3ZAQ7-2
VMA21ENST00000477649.1 linkn.133+670C>T intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.0000265
AC:
3
AN:
113247
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35393
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000917
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:
0.0000375
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
2
AN:
100394
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
35496
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000382
AC:
4
AN:
1047745
Hom.:
0
Cov.:
30
AF XY:
0.00000584
AC XY:
2
AN XY:
342185
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000488
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000265
AC:
3
AN:
113247
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35393
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000917
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000375
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

X-linked myopathy with excessive autophagy Benign:1
Sep 01, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely 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
-0.65
CADD
Benign
9.4
DANN
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
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.

Other links and lift over

dbSNP: rs1268375952; hg19: chrX-150565789; API