X-151404918-G-T

Position:

• chrX-151404918-G-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.166G>T​(p.Ala56Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000927 in 107,839 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000093 (0 hom., 0 hem., cov: 22)
• Consequence: VMA21 NM_001017980.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 (HGNC:):

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=0.11200678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VMA21	NM_001017980.4	c.166G>T	p.Ala56Ser	missense_variant, splice_region_variant	3/3	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1	c.331G>T	p.Ala111Ser	missense_variant, splice_region_variant	3/3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7	c.166G>T	p.Ala56Ser	missense_variant, splice_region_variant	3/3	1	NM_001017980.4	ENSP00000333255.6
VMA21	ENST00000370361.5	c.331G>T	p.Ala111Ser	missense_variant, splice_region_variant	4/4	5		ENSP00000359386.1
VMA21	ENST00000477649.1	n.246G>T		splice_region_variant, non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.00000927 AC: 1 AN: 107839 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 30561

Gnomad AFR AF: 0.0000341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000927 AC: 1 AN: 107839 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 30561

Gnomad4 AFR AF: 0.0000341

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0017	.;T
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.42	.;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.058
Sift	Benign	0.13	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.042	.;B
Vest4		0.13
MutPred		0.51		.;Gain of sheet (P = 0.0028);
MVP		0.38
MPC		0.72
ClinPred		0.36	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs140025330; hg19: chrX-150573390;