rs144796570
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003038.5(SLC1A4):c.1316G>A(p.Gly439Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00078 ( 0 hom. )
Consequence
SLC1A4
NM_003038.5 missense
NM_003038.5 missense
Scores
9
7
1
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
SLC1A4 (HGNC:10942): (solute carrier family 1 member 4) The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.794
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC1A4 | NM_003038.5 | c.1316G>A | p.Gly439Glu | missense_variant | 7/8 | ENST00000234256.4 | |
SLC1A4 | NM_001348406.2 | c.656G>A | p.Gly219Glu | missense_variant | 7/8 | ||
SLC1A4 | NM_001348407.2 | c.656G>A | p.Gly219Glu | missense_variant | 7/8 | ||
SLC1A4 | NM_001193493.2 | c.422G>A | p.Gly141Glu | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC1A4 | ENST00000234256.4 | c.1316G>A | p.Gly439Glu | missense_variant | 7/8 | 1 | NM_003038.5 | P1 | |
LINC02245 | ENST00000653778.1 | n.513+29323C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000361 AC: 55AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000278 AC: 70AN: 251392Hom.: 0 AF XY: 0.000272 AC XY: 37AN XY: 135854
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GnomAD4 exome AF: 0.000779 AC: 1139AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.000743 AC XY: 540AN XY: 727244
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GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 439 of the SLC1A4 protein (p.Gly439Glu). This variant is present in population databases (rs144796570, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SLC1A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 587616). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC1A4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at