Variant 16-19555551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000251143.9(VPS35L):c.89C>T(p.Ala30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,552,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VPS35L
ENST00000251143.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08085626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein
VPS35L	ENST00000251143.9 linkuse as main transcript	c.89C>T	p.Ala30Val	missense_variant	1/31	1	ENSP00000251143
VPS35L	ENST00000542263.5 linkuse as main transcript	c.-179C>T		5_prime_UTR_variant	1/28	2	ENSP00000442468
VPS35L	ENST00000544670.5 linkuse as main transcript	c.-204+231C>T		intron_variant		5	ENSP00000456425
VPS35L	ENST00000539322.5 linkuse as main transcript	c.89C>T	p.Ala30Val	missense_variant, NMD_transcript_variant	1/12	5	ENSP00000438852

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1400704

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

691928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000175

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

Sep 17, 2021

The c.89C>T (p.A30V) alteration is located in exon 1 (coding exon 1) of the C16orf62 gene. This alteration results from a C to T substitution at nucleotide position 89, causing the alanine (A) at amino acid position 30 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.00070

LIST_S2

Benign

0.54

.;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.081

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.020

N;.;N

REVEL

Benign

0.024

Sift

Uncertain

0.027

D;.;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.13

MutPred

0.33

Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);

MVP

0.14

MPC

0.23

ClinPred

0.13

GERP RS

-2.5

gMVP

0.12

Splicing

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