chrX-151397316-G-T

Variant names:

• chrX-151397316-G-T
• NM_001017980.4:c.8G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017980.4(VMA21):​c.8G>T​(p.Arg3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VMA21 NM_001017980.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17792583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001017980.4	c.8G>T	p.Arg3Leu	missense_variant	Exon 1 of 3	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1	c.218+259G>T		intron_variant	Intron 1 of 2		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7	c.8G>T	p.Arg3Leu	missense_variant	Exon 1 of 3	1	NM_001017980.4	ENSP00000333255.6
VMA21	ENST00000370361.5	c.218+259G>T		intron_variant	Intron 2 of 3	5		ENSP00000359386.1
VMA21	ENST00000477649.1	n.133+669G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1047468 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 342012

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8G>T (p.R3L) alteration is located in exon 1 (coding exon 1) of the VMA21 gene. This alteration results from a G to T substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0088	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.076	T
Sift4G	Benign	0.13	T
Polyphen		0.65	P
Vest4		0.41
MutPred		0.22		Gain of methylation at K6 (P = 0.0935);
MVP		0.54
MPC		0.96
ClinPred		0.46	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-150565788;