chr16-89709371-G-C

Variant names:

• chr16-89709371-G-C
• rs2060863971
• NM_004913.3:c.1453C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004913.3(VPS9D1):​c.1453C>G​(p.Pro485Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS9D1	NM_004913.3	c.1453C>G	p.Pro485Ala	missense_variant	Exon 12 of 15	ENST00000389386.8	NP_004904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS9D1	ENST00000389386.8	c.1453C>G	p.Pro485Ala	missense_variant	Exon 12 of 15	1	NM_004913.3	ENSP00000374037.3
VPS9D1	ENST00000561976.5	c.1243C>G	p.Pro415Ala	missense_variant	Exon 11 of 14	1		ENSP00000454244.1
VPS9D1	ENST00000565023.1	c.253C>G	p.Pro85Ala	missense_variant	Exon 3 of 6	5		ENSP00000455792.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1453C>G (p.P485A) alteration is located in exon 12 (coding exon 12) of the VPS9D1 gene. This alteration results from a C to G substitution at nucleotide position 1453, causing the proline (P) at amino acid position 485 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.1	.;M
PhyloP100		4.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.23
Sift	Benign	0.067	T;D
Sift4G	Uncertain	0.031	D;D
Polyphen		1.0	.;D
Vest4		0.54
MutPred		0.48		.;Gain of relative solvent accessibility (P = 0.0217);
MVP		0.42
MPC		0.21
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.48

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

Other links and lift over

dbSNP: rs2060863971; hg19: chr16-89775779;