NM_004913.3:c.461T>C

Variant names:

• chr16-89712687-A-G
• rs539715214
• NM_004913.3:c.461T>C

Variant summary

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

The NM_004913.3(VPS9D1):​c.461T>C​(p.Leu154Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. L154M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92
• 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]

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

ACMG classification

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

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

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.461T>C	p.Leu154Pro	missense	Exon 5 of 15	NP_004904.2	Q9Y2B5-1
	VPS9D1-AS1	NR_036480.1		n.368-2A>G		splice_acceptor intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	ENST00000389386.8	TSL:1 MANE Select	c.461T>C	p.Leu154Pro	missense	Exon 5 of 15	ENSP00000374037.3	Q9Y2B5-1
	VPS9D1	ENST00000561976.5	TSL:1	c.251T>C	p.Leu84Pro	missense	Exon 4 of 14	ENSP00000454244.1	H3BM58
	VPS9D1	ENST00000563798.1	TSL:3	n.129T>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000454889.1	H3BNK1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	M
PhyloP100		5.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.021	D
Polyphen		0.94	P
Vest4		0.79
MutPred		0.16		Gain of loop (P = 0.0079)
MVP		0.14
MPC		0.85
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.78
gMVP		0.64

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: rs539715214; hg19: chr16-89779095;