8-17247414-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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 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	UniProt
VPS37A	NM_152415.3	c.125+45A>G		intron_variant		ENST00000324849.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS37A	ENST00000324849.9	c.125+45A>G		intron_variant		1	NM_152415.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 255 AN: 7082 Hom.: 0 Cov.: 0 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.: 0 AF XY: 0.0173 AC XY: 273 AN XY: 15790

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.: 1 Cov.: 0 AF XY: 0.111 AC XY: 3727 AN XY: 33582

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.: 0 Cov.: 0 AF XY: 0.0310 AC XY: 118 AN XY: 3802

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.: 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

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs1457709223; hg19: chr8-17104923;