rs768244692

Variant names:

• chr16-89709418-C-A
• rs768244692
• NM_004913.3:c.1406G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-89709418-C-A
• chr16-89709418-C-G
• chr16-89709418-C-T

Variant summary

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

The NM_004913.3(VPS9D1):​c.1406G>T​(p.Arg469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R469Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• 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 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.1406G>T	p.Arg469Leu	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.1406G>T	p.Arg469Leu	missense_variant	Exon 12 of 15	1	NM_004913.3	ENSP00000374037.3
VPS9D1	ENST00000561976.5	c.1196G>T	p.Arg399Leu	missense_variant	Exon 11 of 14	1		ENSP00000454244.1
VPS9D1	ENST00000565023.1	c.206G>T	p.Arg69Leu	missense_variant	Exon 3 of 6	5		ENSP00000455792.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 162900 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1364524 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 670428

African (AFR) AF: 0.00 AC: 0 AN: 30534

American (AMR) AF: 0.00 AC: 0 AN: 30870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20178

East Asian (EAS) AF: 0.00 AC: 0 AN: 38926

South Asian (SAS) AF: 0.00 AC: 0 AN: 71590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3960

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072150

Other (OTH) AF: 0.00 AC: 0 AN: 56318

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	.;M
PhyloP100		0.80
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.15
Sift	Benign	0.10	T;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.91	.;P
Vest4		0.72
MutPred		0.46		.;Loss of disorder (P = 0.05);
MVP		0.44
MPC		0.24
ClinPred		0.81	D
GERP RS		2.1
Varity_R		0.18
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768244692; hg19: chr16-89775826; COSMIC: COSV66995465; COSMIC: COSV66995465;