Variant 8-17247377-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152415.3(VPS37A):c.125+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,528,448 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 92 hom. )

Consequence

VPS37A
NM_152415.3 splice_region, intron

Scores

Splicing: ADA: 0.0001464

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.68

Variant links:

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]

VPS37A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 8-17247377-G-A is Benign according to our data. Variant chr8-17247377-G-A is described in ClinVar as [Benign]. Clinvar id is 509802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37A	NM_152415.3 link	c.125+8G>A		splice_region_variant, intron_variant		ENST00000324849.9	NP_689628.2	Q8NEZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37A	ENST00000324849.9 link	c.125+8G>A		splice_region_variant, intron_variant		1	NM_152415.3	ENSP00000318629.4		Q8NEZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

318

AN:

147616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0502

Gnomad SAS

AF:

0.000641

Gnomad FIN

AF:

0.000927

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000341

Gnomad OTH

AF:

0.00247

GnomAD3 exomes

AF:

0.00447

AC:

631

AN:

141312

Hom.:

AF XY:

0.00416

AC XY:

317

AN XY:

76150

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.000503

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0510

Gnomad SAS exome

AF:

0.000846

Gnomad FIN exome

AF:

0.00187

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00291

GnomAD4 exome

AF:

0.00205

AC:

2834

AN:

1380762

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1397

AN XY:

678628

show subpopulations

Gnomad4 AFR exome

AF:

0.000288

Gnomad4 AMR exome

AF:

0.000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0655

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00337

GnomAD4 genome

AF:

0.00215

AC:

317

AN:

147686

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

167

AN XY:

71702

show subpopulations

Gnomad4 AFR

AF:

0.000629

Gnomad4 AMR

AF:

0.000413

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0502

Gnomad4 SAS

AF:

0.000643

Gnomad4 FIN

AF:

0.000927

Gnomad4 NFE

AF:

0.000341

Gnomad4 OTH

AF:

0.00244

Alfa

AF:

0.000366

Hom.:

Bravo

AF:

0.00233

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary spastic paraplegia 53

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Sep 01, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.022

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over