Variant rs1127231 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013245.3(VPS4A):c.861A>G(p.Lys287=) variant causes a synonymous change. The variant allele was found at a frequency of 0.314 in 1,582,594 control chromosomes in the GnomAD database, including 80,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8157 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72228 hom. )

Consequence

VPS4A
NM_013245.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.05

Variant links:

Genes affected

VPS4A (HGNC:13488): (vacuolar protein sorting 4 homolog A) The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]

VPS4A links:

COG8 (HGNC:18623): (component of oligomeric golgi complex 8) This gene encodes a protein that is a component of the conserved oligomeric Golgi (COG) complex, a multiprotein complex that plays a structural role in the Golgi apparatus, and is involved in intracellular membrane trafficking and glycoprotein modification. Mutations in this gene cause congenital disorder of glycosylation, type IIh, a disease that is characterized by under-glycosylated serum proteins, and whose symptoms include severe psychomotor retardation, failure to thrive, seizures, and dairy and wheat product intolerance. [provided by RefSeq, Jul 2008]

COG8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS4A	NM_013245.3 linkuse as main transcript	c.861A>G	p.Lys287=	synonymous_variant	9/11	ENST00000254950.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VPS4A	ENST00000254950.13 linkuse as main transcript	c.861A>G	p.Lys287=	synonymous_variant	9/11	1	NM_013245.3	P1
VPS4A	ENST00000562754.1 linkuse as main transcript	n.577A>G		non_coding_transcript_exon_variant	3/3	2
COG8	ENST00000564419.1 linkuse as main transcript	n.30-14T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
VPS4A	ENST00000564399.1 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48425

AN:

151758

Hom.:

8122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.267

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.0921

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.273

AC:

55461

AN:

202942

Hom.:

8206

AF XY:

0.279

AC XY:

30501

AN XY:

109130

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.0916

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.314

AC:

448563

AN:

1430718

Hom.:

72228

Cov.:

AF XY:

0.315

AC XY:

223509

AN XY:

708718

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.362

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.319

AC:

48516

AN:

151876

Hom.:

8157

Cov.:

AF XY:

0.316

AC XY:

23426

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.383

Gnomad4 AMR

AF:

0.267

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.0923

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.319

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.310

Hom.:

12044

Bravo

AF:

0.319

Asia WGS

AF:

0.287

AC:

997

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.6

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over