8-17247418-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152415.3(VPS37A):c.125+49C>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 0.0082 (0 hom., cov: 0)
  • Exomes 𝑓: 0.063 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS37A NM_152415.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 8-17247418-C-G is Benign according to our data. Variant chr8-17247418-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1194269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS37A	NM_152415.3	c.125+49C>G		intron_variant		ENST00000324849.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS37A	ENST00000324849.9	c.125+49C>G		intron_variant		1	NM_152415.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 227 AN: 27774 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00998

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00698

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00535

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00843

Gnomad OTH AF: 0.0159

GnomAD3 exomes AF: 0.0324 AC: 678 AN: 20932 Hom.: 3 AF XY: 0.0278 AC XY: 360 AN XY: 12934

Gnomad AFR exome AF: 0.0462

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.0485

Gnomad SAS exome AF: 0.0217

Gnomad FIN exome AF: 0.0443

Gnomad NFE exome AF: 0.0243

Gnomad OTH exome AF: 0.0418

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0627 AC: 6582 AN: 104922 Hom.: 13 Cov.: 0 AF XY: 0.0670 AC XY: 3727 AN XY: 55594

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0414

Gnomad4 EAS exome AF: 0.0423

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0720

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00816 AC: 227 AN: 27812 Hom.: 0 Cov.: 0 AF XY: 0.00820 AC XY: 113 AN XY: 13780

Gnomad4 AFR AF: 0.00993

Gnomad4 AMR AF: 0.00694

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.00535

Gnomad4 NFE AF: 0.00843

Gnomad4 OTH AF: 0.0155

Alfa AF: 0.000184 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	9.6
Dann	Benign	0.74

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: rs768919537; hg19: chr8-17104927;