Genetic Variant NM_003053.4:c.293G>T (chr8-20179316-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003053.4(SLC18A1):c.293G>T(p.Ser98Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC18A1
NM_003053.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.888

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0740073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC18A1	NM_003053.4	MANE Select	c.293G>T	p.Ser98Ile	missense	Exon 3 of 16	NP_003044.1	P54219-1
SLC18A1	NM_001135691.3		c.293G>T	p.Ser98Ile	missense	Exon 4 of 17	NP_001129163.1	P54219-1
SLC18A1	NM_001438745.1		c.293G>T	p.Ser98Ile	missense	Exon 3 of 15	NP_001425674.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC18A1	ENST00000276373.10	TSL:1 MANE Select	c.293G>T	p.Ser98Ile	missense	Exon 3 of 16	ENSP00000276373.5	P54219-1
SLC18A1	ENST00000265808.11	TSL:1	c.293G>T	p.Ser98Ile	missense	Exon 4 of 16	ENSP00000265808.7	P54219-3
SLC18A1	ENST00000440926.3	TSL:5	c.293G>T	p.Ser98Ile	missense	Exon 4 of 17	ENSP00000387549.1	P54219-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.0000331

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.97

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.079

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.69

M_CAP

Benign

0.0064

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PhyloP100

-0.89

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

REVEL

Benign

0.012

Sift

Benign

0.41

Sift4G

Benign

0.26

Polyphen

0.076

Vest4

0.33

MutPred

0.48

Loss of glycosylation at S98 (P = 0.0046)

MVP

0.030

MPC

0.0025

ClinPred

0.22

GERP RS

-5.8

Varity_R

0.048

gMVP

0.64

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over