rs886039768

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_021815.5(SLC5A7):​c.143A>G​(p.Asp48Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D48N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SLC5A7
NM_021815.5 missense

Scores

4
8
7

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.87
Variant links:
Genes affected
SLC5A7 (HGNC:14025): (solute carrier family 5 member 7) This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81
PP5
Variant 2-107988298-A-G is Pathogenic according to our data. Variant chr2-107988298-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 265765.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-107988298-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC5A7NM_021815.5 linkuse as main transcriptc.143A>G p.Asp48Gly missense_variant 2/9 ENST00000264047.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC5A7ENST00000264047.3 linkuse as main transcriptc.143A>G p.Asp48Gly missense_variant 2/91 NM_021815.5 P1
SLC5A7ENST00000409059.5 linkuse as main transcriptc.143A>G p.Asp48Gly missense_variant 2/91 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 20 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMOct 07, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T;T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Uncertain
0.097
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Uncertain
-0.10
T
MutationAssessor
Benign
1.6
L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.9
N;N
REVEL
Uncertain
0.60
Sift
Benign
0.23
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.021
B;B
Vest4
0.92
MutPred
0.58
Gain of methylation at R47 (P = 0.0303);Gain of methylation at R47 (P = 0.0303);
MVP
0.83
MPC
1.1
ClinPred
0.65
D
GERP RS
5.8
Varity_R
0.46
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.40
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.40
Position offset: -1

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.

Other links and lift over

dbSNP: rs886039768; hg19: chr2-108604754; API