8-17247410-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152415.3(VPS37A):c.125+41T>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 0.038 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS37A NM_152415.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 8-17247410-T-G is Benign according to our data. Variant chr8-17247410-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1205684.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+41T>G		intron_variant		ENST00000324849.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS37A	ENST00000324849.9	c.125+41T>G		intron_variant		1	NM_152415.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 225 AN: 5868 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.0347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0625

GnomAD3 exomes AF: 0.0278 AC: 649 AN: 23352 Hom.: 0 AF XY: 0.0234 AC XY: 338 AN XY: 14440

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.00815

Gnomad EAS exome AF: 0.0675

Gnomad SAS exome AF: 0.0187

Gnomad FIN exome AF: 0.0336

Gnomad NFE exome AF: 0.0222

Gnomad OTH exome AF: 0.0404

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.116 AC: 5928 AN: 50900 Hom.: 0 Cov.: 0 AF XY: 0.113 AC XY: 3366 AN XY: 29800

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0457

Gnomad4 EAS exome AF: 0.0647

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0697

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0382 AC: 225 AN: 5896 Hom.: 0 Cov.: 0 AF XY: 0.0318 AC XY: 102 AN XY: 3208

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0287

Gnomad4 ASJ AF: 0.0347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0412

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0402

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.000613 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 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	15
Dann	Benign	0.66

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: rs1270448786; hg19: chr8-17104919;