8-17280263-G-T

Variant names:

• chr8-17280263-G-T
• NM_152415.3:c.866G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152415.3(VPS37A):​c.866G>T​(p.Ser289Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: VPS37A NM_152415.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

Genes affected

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

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=0.19675764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS37A	NM_152415.3	c.866G>T	p.Ser289Ile	missense_variant	Exon 8 of 12	ENST00000324849.9	NP_689628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS37A	ENST00000324849.9	c.866G>T	p.Ser289Ile	missense_variant	Exon 8 of 12	1	NM_152415.3	ENSP00000318629.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460594 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 726516

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: 0.00000540

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	0.084
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.28
MutPred		0.44		Loss of disorder (P = 0.0143);.;.;
MVP		0.13
MPC		0.015
ClinPred		0.45	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.12
gMVP		0.27

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: chr8-17137772;