rs765146515

Variant names:

• chr16-89709314-C-G
• rs765146515
• NM_004913.3:c.1510G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-89709314-C-G
• chr16-89709314-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004913.3(VPS9D1):​c.1510G>C​(p.Ala504Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086203694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS9D1	NM_004913.3	c.1510G>C	p.Ala504Pro	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.1510G>C	p.Ala504Pro	missense_variant	Exon 12 of 15	1	NM_004913.3	ENSP00000374037.3
VPS9D1	ENST00000561976.5	c.1300G>C	p.Ala434Pro	missense_variant	Exon 11 of 14	1		ENSP00000454244.1
VPS9D1	ENST00000565023.1	c.310G>C	p.Ala104Pro	missense_variant	Exon 3 of 6	5		ENSP00000455792.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000421 AC: 1 AN: 237562 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129972

Gnomad AFR exome AF: 0.0000674

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452560 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722586

Gnomad4 AFR exome AF: 0.0000300

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.029	.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.032
Sift	Benign	0.19	T;T
Sift4G	Benign	0.095	T;T
Polyphen		0.38	.;B
Vest4		0.20
MutPred		0.36		.;Gain of glycosylation at A504 (P = 0.0347);
MVP		0.048
MPC		0.23
ClinPred		0.050	T
GERP RS		-1.5
Varity_R		0.10
gMVP		0.46

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

Other links and lift over

dbSNP: rs765146515; hg19: chr16-89775722;