16-89710657-C-A

Variant names:

• chr16-89710657-C-A
• rs756169321
• NM_004913.3:c.1187G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004913.3(VPS9D1):​c.1187G>T​(p.Gly396Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G396D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18454617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004913.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	NM_004913.3	MANE Select	c.1187G>T	p.Gly396Val	missense	Exon 10 of 15	NP_004904.2	Q9Y2B5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	ENST00000389386.8	TSL:1 MANE Select	c.1187G>T	p.Gly396Val	missense	Exon 10 of 15	ENSP00000374037.3	Q9Y2B5-1
	VPS9D1	ENST00000561976.5	TSL:1	c.977G>T	p.Gly326Val	missense	Exon 9 of 14	ENSP00000454244.1	H3BM58
	VPS9D1	ENST00000906741.1		c.1187G>T	p.Gly396Val	missense	Exon 10 of 15	ENSP00000576800.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.12
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.043
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		0.84	P
Vest4		0.33
MutPred		0.28		Gain of helix (P = 0.0425)
MVP		0.24
MPC		0.23
ClinPred		0.22	T
GERP RS		2.8
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.29

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: rs756169321; hg19: chr16-89777065;