NM_004913.3:c.1346C>G

Variant names:

• chr16-89709819-G-C
• NM_004913.3:c.1346C>G

Variant summary

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

The NM_004913.3(VPS9D1):​c.1346C>G​(p.Pro449Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

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 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.1346C>G	p.Pro449Arg	missense_variant	Exon 11 of 15	ENST00000389386.8	NP_004904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS9D1	ENST00000389386.8	c.1346C>G	p.Pro449Arg	missense_variant	Exon 11 of 15	1	NM_004913.3	ENSP00000374037.3
VPS9D1	ENST00000561976.5	c.1136C>G	p.Pro379Arg	missense_variant	Exon 10 of 14	1		ENSP00000454244.1
VPS9D1	ENST00000565023.1	c.146C>G	p.Pro49Arg	missense_variant	Exon 2 of 6	5		ENSP00000455792.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461566 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727118

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.077
Sift	Benign	0.092	T;T
Sift4G	Uncertain	0.018	D;D
Polyphen		0.88	.;P
Vest4		0.61
MutPred		0.47		.;Loss of loop (P = 0.0512);
MVP		0.52
MPC		0.30
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.18
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89776227;