16-19555727-A-C

Position:

• chr16-19555727-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000417362.7(VPS35L):​c.-3A>C variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS35L ENST00000417362.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28532368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS35L	NM_020314.7	c.-3A>C		5_prime_UTR_variant	1/31	ENST00000417362.7	NP_064710.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS35L	ENST00000417362.7	c.-3A>C		5_prime_UTR_variant	1/31	1	NM_020314.7	ENSP00000395973	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.265A>C (p.K89Q) alteration is located in exon 1 (coding exon 1) of the C16orf62 gene. This alteration results from a A to C substitution at nucleotide position 265, causing the lysine (K) at amino acid position 89 to be replaced by a glutamine (Q). 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	0.0022	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T;T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D;N;N;N
PROVEAN	Benign	0.090	N;.;N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.51
MutPred		0.32		Loss of methylation at K89 (P = 0.0307);Loss of methylation at K89 (P = 0.0307);Loss of methylation at K89 (P = 0.0307);
MVP		0.45
MPC		0.29
ClinPred		0.97	D
GERP RS		4.6
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19567049;