NM_016516.3:c.2286C>T

Variant names:

• chr2-63914230-G-A
• rs1558987428
• NM_016516.3:c.2286C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016516.3(VPS54):​c.2286C>T​(p.Ile762Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS54 NM_016516.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

Genes affected

VPS54 (HGNC:18652): (VPS54 subunit of GARP complex) This gene encodes for a protein that in yeast forms part of a trimeric vacuolar-protein-sorting complex that is required for retrograde transport of proteins from prevacuoles to the late Golgi compartment. As in yeast, mammalian Vps54 proteins contain a coiled-coil region and dileucine motifs. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.49 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS54	NM_016516.3	c.2286C>T	p.Ile762Ile	synonymous_variant	Exon 17 of 23	ENST00000272322.9	NP_057600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS54	ENST00000272322.9	c.2286C>T	p.Ile762Ile	synonymous_variant	Exon 17 of 23	5	NM_016516.3	ENSP00000272322.4
VPS54	ENST00000409558.8	c.2250C>T	p.Ile750Ile	synonymous_variant	Exon 17 of 23	1		ENSP00000386980.3
VPS54	ENST00000354504.7	c.1827C>T	p.Ile609Ile	synonymous_variant	Exon 14 of 20	1		ENSP00000346499.3
VPS54	ENST00000416400.1	n.168C>T		non_coding_transcript_exon_variant	Exon 3 of 10	1		ENSP00000414725.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.3
DANN	Benign	0.68

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: rs1558987428; hg19: chr2-64141364;