8-20179316-C-T

Variant names:

• chr8-20179316-C-T
• NM_003053.4:c.293G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003053.4(SLC18A1):​c.293G>A​(p.Ser98Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S98T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC18A1 NM_003053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05135128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.293G>A	p.Ser98Asn	missense_variant	Exon 3 of 16	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.293G>A	p.Ser98Asn	missense_variant	Exon 3 of 16	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461872 Hom.: 0 Cov.: 58 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.24
DEOGEN2	Benign	0.037	.;T;T;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.48	.;.;T;T;T;.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.051	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.89	L;L;L;L;L;L;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.090	N;N;N;N;N;N;N
REVEL	Benign	0.0030
Sift	Benign	0.37	T;T;T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T;T;T
Polyphen		0.0010	.;B;B;.;.;.;.
Vest4		0.083
MutPred		0.35		Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);Loss of glycosylation at S98 (P = 0.0046);
MVP		0.030
MPC		0.0023
ClinPred		0.088	T
GERP RS		-5.8
Varity_R		0.037
gMVP		0.51

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: chr8-20036827;