Variant 8-17286321-G-C 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.1114-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,594,638 control chromosomes in the GnomAD database, including 89,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13117 hom., cov: 32)

Exomes 𝑓: 0.31 ( 76447 hom. )

Consequence

VPS37A
NM_152415.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20

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:

VPS37A (HGNC:):

VPS37A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-17286321-G-C is Benign according to our data. Variant chr8-17286321-G-C is described in ClinVar as [Benign]. Clinvar id is 1247255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37A	NM_152415.3 linkuse as main transcript	c.1114-26G>C		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 linkuse as main transcript	c.1114-26G>C		intron_variant		1	NM_152415.3	ENSP00000318629.4		Q8NEZ2-1

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

59022

AN:

151932

Hom.:

13086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.386

AC:

92382

AN:

239030

Hom.:

20175

AF XY:

0.378

AC XY:

48922

AN XY:

129258

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.381

Gnomad EAS exome

AF:

0.705

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.305

AC:

440049

AN:

1442588

Hom.:

76447

Cov.:

AF XY:

0.308

AC XY:

221397

AN XY:

718032

show subpopulations

Gnomad4 AFR exome

AF:

0.573

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.745

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.389

AC:

59104

AN:

152050

Hom.:

13117

Cov.:

AF XY:

0.396

AC XY:

29403

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.559

Gnomad4 AMR

AF:

0.436

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.717

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.285

Hom.:

4162

Bravo

AF:

0.408

Asia WGS

AF:

0.599

AC:

2080

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Hereditary spastic paraplegia 53

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.65

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

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