Variant 8-20171129-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003053.4(SLC18A1):c.832C>G(p.Leu278Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLC18A1
NM_003053.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

SLC18A1 (HGNC:10934): (solute carrier family 18 member A1) The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]

SLC18A1 links:

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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	UniProt
SLC18A1	NM_003053.4 linkuse as main transcript	c.832C>G	p.Leu278Val	missense_variant	8/16	ENST00000276373.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A1	ENST00000276373.10 linkuse as main transcript	c.832C>G	p.Leu278Val	missense_variant	8/16	1	NM_003053.4	P1	P54219-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251330

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727234

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.832C>G (p.L278V) alteration is located in exon 8 (coding exon 7) of the SLC18A1 gene. This alteration results from a C to G substitution at nucleotide position 832, causing the leucine (L) at amino acid position 278 to be replaced by a valine (V). 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

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.090

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.70

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

3.0

M;M;M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.7

D;D;D;D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;T;T;T;D;T;D

Sift4G

Benign

0.081

T;T;T;D;T;D;D

Polyphen

1.0

.;D;D;.;.;.;.

Vest4

0.72

MutPred

0.60

Gain of catalytic residue at L278 (P = 0.0657);Gain of catalytic residue at L278 (P = 0.0657);Gain of catalytic residue at L278 (P = 0.0657);Gain of catalytic residue at L278 (P = 0.0657);Gain of catalytic residue at L278 (P = 0.0657);Gain of catalytic residue at L278 (P = 0.0657);.;

MVP

0.64

MPC

0.0065

ClinPred

0.94

GERP RS

4.8

Varity_R

0.53

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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