16-89710906-C-T

Position:

• chr16-89710906-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.938G>A​(p.Cys313Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS9D1 NM_004913.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.08898771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS9D1	NM_004913.3	c.938G>A	p.Cys313Tyr	missense_variant	10/15	ENST00000389386.8	NP_004904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS9D1	ENST00000389386.8	c.938G>A	p.Cys313Tyr	missense_variant	10/15	1	NM_004913.3	ENSP00000374037	A2
VPS9D1	ENST00000561976.5	c.728G>A	p.Cys243Tyr	missense_variant	9/14	1		ENSP00000454244	P2
VPS9D1	ENST00000568691.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1340316 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 657130

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.938G>A (p.C313Y) alteration is located in exon 10 (coding exon 10) of the VPS9D1 gene. This alteration results from a G to A substitution at nucleotide position 938, causing the cysteine (C) at amino acid position 313 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
MutationTaster	Benign	0.94	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.095
Sift	Benign	1.0	T;T
Sift4G	Benign	0.086	T;T
Polyphen		0.0	.;B
Vest4		0.21
MutPred		0.38		.;Gain of solvent accessibility (P = 0.0042);
MVP		0.31
MPC		0.30
ClinPred		0.028	T
GERP RS		2.2
Varity_R		0.032
gMVP		0.23

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: chr16-89777314;