19-49432903-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020309.4(SLC17A7):​c.925G>A​(p.Val309Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,451,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

SLC17A7
NM_020309.4 missense

Scores

7
11
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC17A7NM_020309.4 linkc.925G>A p.Val309Met missense_variant Exon 8 of 12 ENST00000221485.8 NP_064705.1 Q9P2U7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC17A7ENST00000221485.8 linkc.925G>A p.Val309Met missense_variant Exon 8 of 12 1 NM_020309.4 ENSP00000221485.2 Q9P2U7-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000827
AC:
12
AN:
1451602
Hom.:
0
Cov.:
35
AF XY:
0.00000832
AC XY:
6
AN XY:
720776
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000993
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.925G>A (p.V309M) alteration is located in exon 8 (coding exon 8) of the SLC17A7 gene. This alteration results from a G to A substitution at nucleotide position 925, causing the valine (V) at amino acid position 309 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
D;.
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Uncertain
0.65
D;D
MetaSVM
Uncertain
-0.036
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-2.5
D;.
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.78
MutPred
0.52
Loss of catalytic residue at V309 (P = 0.1286);.;
MVP
0.043
MPC
2.1
ClinPred
0.96
D
GERP RS
4.0
Varity_R
0.85
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: -20

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: rs781639940; hg19: chr19-49936160; COSMIC: COSV55548328; COSMIC: COSV55548328; API