chr16-69316132-A-C

Variant names:

• chr16-69316132-A-C
• rs3817030
• NM_013245.3:c.133+13A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013245.3(VPS4A):​c.133+13A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,612,764 control chromosomes in the GnomAD database, including 52,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6410 hom., cov: 31)
  • Exomes 𝑓: 0.25 (46018 hom.)
• Consequence: VPS4A NM_013245.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.99

Genes affected

VPS4A (HGNC:13488): (vacuolar protein sorting 4 homolog A) The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]

ENSG00000260914 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-69316132-A-C is Benign according to our data. Variant chr16-69316132-A-C is described in ClinVar as [Benign]. Clinvar id is 1246081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS4A	NM_013245.3	c.133+13A>C		intron_variant	Intron 2 of 10	ENST00000254950.13	NP_037377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS4A	ENST00000254950.13	c.133+13A>C		intron_variant	Intron 2 of 10	1	NM_013245.3	ENSP00000254950.11
ENSG00000260914	ENST00000570054.3	c.205+13A>C		intron_variant	Intron 2 of 9	5		ENSP00000461295.3

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41998 AN: 151894 Hom.: 6389 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.212 AC: 52587 AN: 247992 AF XY: 0.210

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.0509

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.245 AC: 357913 AN: 1460752 Hom.: 46018 Cov.: 34 AF XY: 0.242 AC XY: 176000 AN XY: 726630

Gnomad4 AFR exome AF: 0.395 AC: 13231 AN: 33476

Gnomad4 AMR exome AF: 0.153 AC: 6837 AN: 44704

Gnomad4 ASJ exome AF: 0.206 AC: 5377 AN: 26120

Gnomad4 EAS exome AF: 0.0622 AC: 2468 AN: 39700

Gnomad4 SAS exome AF: 0.146 AC: 12559 AN: 86254

Gnomad4 FIN exome AF: 0.237 AC: 12509 AN: 52722

Gnomad4 NFE exome AF: 0.260 AC: 288676 AN: 1111662

Gnomad4 Remaining exome AF: 0.242 AC: 14594 AN: 60352

GnomAD4 genome AF: 0.277 AC: 42054 AN: 152012 Hom.: 6410 Cov.: 31 AF XY: 0.271 AC XY: 20153 AN XY: 74290

Gnomad4 AFR AF: 0.391 AC: 0.3909 AN: 0.3909

Gnomad4 AMR AF: 0.221 AC: 0.220819 AN: 0.220819

Gnomad4 ASJ AF: 0.210 AC: 0.210253 AN: 0.210253

Gnomad4 EAS AF: 0.0489 AC: 0.0489362 AN: 0.0489362

Gnomad4 SAS AF: 0.129 AC: 0.129461 AN: 0.129461

Gnomad4 FIN AF: 0.227 AC: 0.227195 AN: 0.227195

Gnomad4 NFE AF: 0.259 AC: 0.259352 AN: 0.259352

Gnomad4 OTH AF: 0.272 AC: 0.271822 AN: 0.271822

Alfa AF: 0.245 Hom.: 5090

Bravo AF: 0.280

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3817030; hg19: chr16-69350035;