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20-2860127-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_022575.4(VPS16):c.216C>T(p.Ser72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,888 control chromosomes in the GnomAD database, including 20,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1562 hom., cov: 32)
Exomes 𝑓: 0.16 ( 19394 hom. )

Consequence

VPS16
NM_022575.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.79
Variant links:
Genes affected
VPS16 (HGNC:14584): (VPS16 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-2860127-C-T is Benign according to our data. Variant chr20-2860127-C-T is described in ClinVar as [Benign]. Clinvar id is 1242073.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.79 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VPS16NM_022575.4 linkuse as main transcriptc.216C>T p.Ser72= synonymous_variant 3/24 ENST00000380445.8
VPS16NM_080413.3 linkuse as main transcriptc.216C>T p.Ser72= synonymous_variant 3/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VPS16ENST00000380445.8 linkuse as main transcriptc.216C>T p.Ser72= synonymous_variant 3/241 NM_022575.4 P1Q9H269-1
VPS16ENST00000380469.7 linkuse as main transcriptc.216C>T p.Ser72= synonymous_variant 3/202 Q9H269-2
VPS16ENST00000417508.1 linkuse as main transcriptc.15+320C>T intron_variant 5
VPS16ENST00000453689.5 linkuse as main transcriptc.15+320C>T intron_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.129
AC:
19571
AN:
151994
Hom.:
1560
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0439
Gnomad AMI
AF:
0.163
Gnomad AMR
AF:
0.126
Gnomad ASJ
AF:
0.166
Gnomad EAS
AF:
0.222
Gnomad SAS
AF:
0.281
Gnomad FIN
AF:
0.161
Gnomad MID
AF:
0.161
Gnomad NFE
AF:
0.156
Gnomad OTH
AF:
0.119
GnomAD3 exomes
AF:
0.165
AC:
41375
AN:
251244
Hom.:
3867
AF XY:
0.171
AC XY:
23279
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.0391
Gnomad AMR exome
AF:
0.119
Gnomad ASJ exome
AF:
0.174
Gnomad EAS exome
AF:
0.237
Gnomad SAS exome
AF:
0.266
Gnomad FIN exome
AF:
0.177
Gnomad NFE exome
AF:
0.154
Gnomad OTH exome
AF:
0.167
GnomAD4 exome
AF:
0.157
AC:
228823
AN:
1461774
Hom.:
19394
Cov.:
34
AF XY:
0.161
AC XY:
116737
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0413
Gnomad4 AMR exome
AF:
0.118
Gnomad4 ASJ exome
AF:
0.171
Gnomad4 EAS exome
AF:
0.198
Gnomad4 SAS exome
AF:
0.264
Gnomad4 FIN exome
AF:
0.174
Gnomad4 NFE exome
AF:
0.150
Gnomad4 OTH exome
AF:
0.158
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.129
AC:
19565
AN:
152114
Hom.:
1562
Cov.:
32
AF XY:
0.132
AC XY:
9815
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0438
Gnomad4 AMR
AF:
0.125
Gnomad4 ASJ
AF:
0.166
Gnomad4 EAS
AF:
0.222
Gnomad4 SAS
AF:
0.279
Gnomad4 FIN
AF:
0.161
Gnomad4 NFE
AF:
0.156
Gnomad4 OTH
AF:
0.121
Alfa
AF:
0.149
Hom.:
2985
Bravo
AF:
0.116
Asia WGS
AF:
0.256
AC:
888
AN:
3478
EpiCase
AF:
0.156
EpiControl
AF:
0.154

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
3.9
Dann
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs3818605; hg19: chr20-2840773; COSMIC: COSV66792625; COSMIC: COSV66792625; API