chr16-77876450-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020927.3(VAT1L):ā€‹c.803C>Gā€‹(p.Pro268Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

VAT1L
NM_020927.3 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50
Variant links:
Genes affected
VAT1L (HGNC:29315): (vesicle amine transport 1 like) Predicted to enable oxidoreductase activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VAT1LNM_020927.3 linkuse as main transcriptc.803C>G p.Pro268Arg missense_variant 5/9 ENST00000302536.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VAT1LENST00000302536.3 linkuse as main transcriptc.803C>G p.Pro268Arg missense_variant 5/91 NM_020927.3 P1
VAT1LENST00000563850.1 linkuse as main transcriptn.224C>G non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251482
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461876
Hom.:
0
Cov.:
30
AF XY:
0.0000138
AC XY:
10
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.0000126
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74318
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
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsMar 21, 2022The c.803C>G (p.P268R) alteration is located in exon 5 (coding exon 5) of the VAT1L gene. This alteration results from a C to G substitution at nucleotide position 803, causing the proline (P) at amino acid position 268 to be replaced by an arginine (R). 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
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.073
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-8.7
D
REVEL
Uncertain
0.56
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.94
MutPred
0.67
Gain of methylation at P268 (P = 0.0303);
MVP
0.49
MPC
0.55
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.93
gMVP
0.91

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.

Other links and lift over

dbSNP: rs770123756; hg19: chr16-77910347; API