Variant 8-17247414-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_152415.3(VPS37A):c.125+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.036 ( 0 hom., cov: 0)

Exomes 𝑓: 0.12 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

VPS37A
NM_152415.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0300

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 8-17247414-A-G is Benign according to our data. Variant chr8-17247414-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1214042.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37A	NM_152415.3 linkuse as main transcript	c.125+45A>G		intron_variant		ENST00000324849.9	NP_689628.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37A	ENST00000324849.9 linkuse as main transcript	c.125+45A>G		intron_variant		1	NM_152415.3	ENSP00000318629	P1	Q8NEZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

255

AN:

7082

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0396

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.0242

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0208

AC:

524

AN:

25236

Hom.:

AF XY:

0.0173

AC XY:

273

AN XY:

15790

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.0916

Gnomad ASJ exome

AF:

0.00711

Gnomad EAS exome

AF:

0.0623

Gnomad SAS exome

AF:

0.0147

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.116

AC:

6598

AN:

56950

Hom.:

Cov.:

AF XY:

0.111

AC XY:

3727

AN XY:

33582

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0426

Gnomad4 EAS exome

AF:

0.0750

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0359

AC:

255

AN:

7112

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

118

AN XY:

3802

show subpopulations

Gnomad4 AFR

AF:

0.0509

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0396

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0242

Gnomad4 NFE

AF:

0.0358

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.00159

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.76

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

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