Variant 16-19682217-T-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 ENST00000417362.7(VPS35L):c.2362-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,607,660 control chromosomes in the GnomAD database, including 1,043 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 456 hom., cov: 32)

Exomes 𝑓: 0.015 ( 587 hom. )

Consequence

VPS35L
ENST00000417362.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003938

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

VPS35L (HGNC:24641): (VPS35 endosomal protein sorting factor like) Involved in Golgi to plasma membrane transport and endocytic recycling. Located in endosome. Implicated in Ritscher-Schinzel syndrome. [provided by Alliance of Genome Resources, Apr 2022]

VPS35L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-19682217-T-C is Benign according to our data. Variant chr16-19682217-T-C is described in ClinVar as [Benign]. Clinvar id is 1249421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS35L	NM_020314.7 linkuse as main transcript	c.2362-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000417362.7	NP_064710.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
VPS35L	ENST00000417362.7 linkuse as main transcript	c.2362-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_020314.7	ENSP00000395973	P1	Q7Z3J2-1
VPS35L	ENST00000251143.9 linkuse as main transcript	c.2629-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000251143
VPS35L	ENST00000543152.5 linkuse as main transcript	c.1609-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000457973
VPS35L	ENST00000542263.5 linkuse as main transcript	c.2083-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000442468

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7417

AN:

152142

Hom.:

454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0412

GnomAD3 exomes

AF:

0.0235

AC:

5828

AN:

248160

Hom.:

228

AF XY:

0.0226

AC XY:

3029

AN XY:

134124

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0356

Gnomad FIN exome

AF:

0.00556

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0150

AC:

21820

AN:

1455400

Hom.:

587

Cov.:

AF XY:

0.0155

AC XY:

11195

AN XY:

723170

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0362

Gnomad4 FIN exome

AF:

0.00589

Gnomad4 NFE exome

AF:

0.00955

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0489

AC:

7440

AN:

152260

Hom.:

456

Cov.:

AF XY:

0.0482

AC XY:

3592

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0259

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0373

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0292

Hom.:

Bravo

AF:

0.0539

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 13, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

dbscSNV1_RF

Benign

0.0

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

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