Genetic Variant VPS9D1:p.Asp67Ala (chr16-89716798-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004913.3(VPS9D1):c.200A>C(p.Asp67Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000278 in 1,440,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS9D1
NM_004913.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

VPS9D1 (HGNC:13526): (VPS9 domain containing 1) Enables identical protein binding activity. Predicted to be involved in ATP synthesis coupled proton transport. [provided by Alliance of Genome Resources, Apr 2022]

VPS9D1 links:

VPS9D1-AS1 (HGNC:48915): (VPS9D1 antisense RNA 1)

VPS9D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3076101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS9D1	NM_004913.3 link	c.200A>C	p.Asp67Ala	missense_variant	Exon 3 of 15	ENST00000389386.8	NP_004904.2	Q9Y2B5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS9D1	ENST00000389386.8 link	c.200A>C	p.Asp67Ala	missense_variant	Exon 3 of 15	1	NM_004913.3	ENSP00000374037.3	Q9Y2B5-1
VPS9D1	ENST00000561976.5 link	c.-11A>C		5_prime_UTR_variant	Exon 2 of 14	1		ENSP00000454244.1	H3BM58
VPS9D1	ENST00000563798.1 link	n.99+3965A>C		intron_variant	Intron 1 of 5	3		ENSP00000454889.1	H3BNK1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152088

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

GnomAD3 exomes

AF:

0.00000444

AC:

AN:

225442

Hom.:

AF XY:

0.00000806

AC XY:

AN XY:

124086

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:

0.00000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1440396

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716812

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:

0.00000271

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74268

Gnomad4 AFR

AF:

0.00

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

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

0.091

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

REVEL

Benign

0.24

Sift

Uncertain

0.014

Sift4G

Uncertain

0.016

Polyphen

0.67

Vest4

0.42

MutPred

0.14

Loss of loop (P = 0.0203);

MVP

0.47

MPC

0.33

ClinPred

0.89

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.24

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