16-77825351-G-A

Variant summary

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

The NM_020927.3(VAT1L):​c.469G>A​(p.Glu157Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

VAT1L
NM_020927.3 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
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 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
VAT1LNM_020927.3 linkuse as main transcriptc.469G>A p.Glu157Lys missense_variant 3/9 ENST00000302536.3 NP_065978.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VAT1LENST00000302536.3 linkuse as main transcriptc.469G>A p.Glu157Lys missense_variant 3/91 NM_020927.3 ENSP00000303129 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152170
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00000398
AC:
1
AN:
251410
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152170
Hom.:
0
Cov.:
30
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.0000151
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

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 GeneticsJan 30, 2024The c.469G>A (p.E157K) alteration is located in exon 3 (coding exon 3) of the VAT1L gene. This alteration results from a G to A substitution at nucleotide position 469, causing the glutamic acid (E) at amino acid position 157 to be replaced by a lysine (K). 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
Uncertain
0.51
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.24
T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.067
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.023
D
Polyphen
0.99
D
Vest4
0.91
MVP
0.46
MPC
0.19
ClinPred
0.83
D
GERP RS
6.0
Varity_R
0.71
gMVP
0.92

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: rs374055734; hg19: chr16-77859248; API