16-77884737-C-A

Variant summary

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

The NM_020927.3(VAT1L):c.1012C>A(p.Leu338Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VAT1L NM_020927.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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]

ACMG classification

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	UniProt
VAT1L	NM_020927.3	c.1012C>A	p.Leu338Ile	missense_variant	7/9	ENST00000302536.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAT1L	ENST00000302536.3	c.1012C>A	p.Leu338Ile	missense_variant	7/9	1	NM_020927.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447550 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719190

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Dec 28, 2022

The c.1012C>A (p.L338I) alteration is located in exon 7 (coding exon 7) of the VAT1L gene. This alteration results from a C to A substitution at nucleotide position 1012, causing the leucine (L) at amino acid position 338 to be replaced by an isoleucine (I). 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	Benign	0.24
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.085
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.20
Sift	Benign	0.27	T
Sift4G	Benign	0.37	T
Polyphen		0.22	B
Vest4		0.68
MutPred		0.53		Gain of MoRF binding (P = 0.0964);
MVP		0.20
MPC		0.23
ClinPred		0.62	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.62

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: chr16-77918634;