NM_004913.3:c.1316A>G

Variant names:

• chr16-89709849-T-C
• rs372981873
• NM_004913.3:c.1316A>G

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.1316A>G​(p.Lys439Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• Publications: 1 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=0.15084639).

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.1316A>G	p.Lys439Arg	missense	Exon 11 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.1316A>G	p.Lys439Arg	missense	Exon 11 of 15	ENSP00000374037.3	Q9Y2B5-1
	VPS9D1	ENST00000561976.5	TSL:1	c.1106A>G	p.Lys369Arg	missense	Exon 10 of 14	ENSP00000454244.1	H3BM58
	VPS9D1	ENST00000906741.1		c.1316A>G	p.Lys439Arg	missense	Exon 11 of 15	ENSP00000576800.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000522 AC: 13 AN: 249118 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.0000885

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000760 AC: 111 AN: 1461468 Hom.: 0 Cov.: 31 AF XY: 0.0000784 AC XY: 57 AN XY: 727066

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1111876

Other (OTH) AF: 0.0000828 AC: 5 AN: 60382

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000236 AC: 1

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.0000660 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Benign	0.0051
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.083
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		0.29	B
Vest4		0.39
MVP		0.29
MPC		0.19
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.16
gMVP		0.44
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs372981873; hg19: chr16-89776257;