20-38725057-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080552.3(SLC32A1):​c.333C>G​(p.His111Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC32A1
NM_080552.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.833
Variant links:
Genes affected
SLC32A1 (HGNC:11018): (solute carrier family 32 member 1) The protein encoded by this gene is an integral membrane protein involved in gamma-aminobutyric acid (GABA) and glycine uptake into synaptic vesicles. The encoded protein is a member of amino acid/polyamine transporter family II. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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=0.0279001).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC32A1NM_080552.3 linkc.333C>G p.His111Gln missense_variant Exon 1 of 2 ENST00000217420.2 NP_542119.1 Q9H598

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC32A1ENST00000217420.2 linkc.333C>G p.His111Gln missense_variant Exon 1 of 2 1 NM_080552.3 ENSP00000217420.1 Q9H598

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SLC32A1: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.1
DANN
Benign
0.81
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.028
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.55
N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.066
Sift
Benign
0.63
T
Sift4G
Benign
0.59
T
Polyphen
0.0
B
Vest4
0.071
MutPred
0.35
Gain of methylation at K113 (P = 0.0829);
MVP
0.41
ClinPred
0.077
T
GERP RS
-3.3
Varity_R
0.053
gMVP
0.16

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: chr20-37353700; API