Variant 16-19682271-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020314.7(VPS35L):c.2408A>T(p.Asn803Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000379 in 1,614,018 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

VPS35L
NM_020314.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

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:

VPS35L (HGNC:):

VPS35L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS35L	NM_020314.7 linkuse as main transcript	c.2408A>T	p.Asn803Ile	missense_variant	28/31	ENST00000417362.7	NP_064710.5	Q7Z3J2-1E7EWW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VPS35L	ENST00000417362.7 linkuse as main transcript	c.2408A>T	p.Asn803Ile	missense_variant	28/31	1	NM_020314.7	ENSP00000395973.3	Q7Z3J2-1
VPS35L	ENST00000251143.9 linkuse as main transcript	c.2675A>T	p.Asn892Ile	missense_variant	28/31	1		ENSP00000251143.6	E7EWW0
VPS35L	ENST00000543152.5 linkuse as main transcript	c.1655A>T	p.Asn552Ile	missense_variant	22/25	1		ENSP00000457973.1	H3BV68
VPS35L	ENST00000542263.5 linkuse as main transcript	c.2129A>T	p.Asn710Ile	missense_variant	25/28	2		ENSP00000442468.2	F5H7K1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000302

AC:

AN:

251458

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000394

AC:

576

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

273

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000237

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000454

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.2675A>T (p.N892I) alteration is located in exon 28 (coding exon 28) of the C16orf62 gene. This alteration results from a A to T substitution at nucleotide position 2675, causing the asparagine (N) at amino acid position 892 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T;.;.;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

.;D;D;D;D;D

M_CAP

Uncertain

0.093

MetaRNN

Uncertain

0.66

D;D;D;D;D;D

MetaSVM

Benign

-0.53

PROVEAN

Pathogenic

-6.2

D;.;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0050

D;.;D;T;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;.;.

Vest4

0.91

MVP

0.59

MPC

0.75

ClinPred

0.41

GERP RS

4.3

gMVP

0.67

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

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