chr19-49430575-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_020309.4(SLC17A7):c.1627G>A(p.Ala543Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000602 in 1,610,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000060 ( 0 hom. )
Consequence
SLC17A7
NM_020309.4 missense
NM_020309.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
SLC17A7 (HGNC:16704): (solute carrier family 17 member 7) The protein encoded by this gene is a vesicle-bound, sodium-dependent phosphate transporter that is specifically expressed in the neuron-rich regions of the brain. It is preferentially associated with the membranes of synaptic vesicles and functions in glutamate transport. The protein shares 82% identity with the differentiation-associated Na-dependent inorganic phosphate cotransporter and they appear to form a distinct class within the Na+/Pi cotransporter family. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, SLC17A7
BP4
Computational evidence support a benign effect (MetaRNN=0.071489275).
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC17A7 | NM_020309.4 | c.1627G>A | p.Ala543Thr | missense_variant | 12/12 | ENST00000221485.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC17A7 | ENST00000221485.8 | c.1627G>A | p.Ala543Thr | missense_variant | 12/12 | 1 | NM_020309.4 | P1 | |
SLC17A7 | ENST00000600601.5 | c.1426G>A | p.Ala476Thr | missense_variant | 12/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 151926Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000862 AC: 21AN: 243728Hom.: 0 AF XY: 0.0000829 AC XY: 11AN XY: 132756
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GnomAD4 exome AF: 0.0000603 AC: 88AN: 1458162Hom.: 0 Cov.: 32 AF XY: 0.0000689 AC XY: 50AN XY: 725272
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GnomAD4 genome AF: 0.0000592 AC: 9AN: 152044Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74316
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.1627G>A (p.A543T) alteration is located in exon 12 (coding exon 12) of the SLC17A7 gene. This alteration results from a G to A substitution at nucleotide position 1627, causing the alanine (A) at amino acid position 543 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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