chr19-49430671-C-T

Variant names:

• chr19-49430671-C-T
• rs145455204
• NM_020309.4:c.1531G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020309.4(SLC17A7):​c.1531G>A​(p.Val511Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V511F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC17A7 NM_020309.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03457269).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A7	NM_020309.4	c.1531G>A	p.Val511Ile	missense_variant	Exon 12 of 12	ENST00000221485.8	NP_064705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A7	ENST00000221485.8	c.1531G>A	p.Val511Ile	missense_variant	Exon 12 of 12	1	NM_020309.4	ENSP00000221485.2
SLC17A7	ENST00000600601.5	c.1330G>A	p.Val444Ile	missense_variant	Exon 12 of 12	2		ENSP00000470338.1
SLC17A7	ENST00000600672.5	n.*84G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250552 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135686

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000191 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.80	T;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.66	N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.27	N;.
REVEL	Benign	0.053
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;.
Vest4		0.050
MutPred		0.18		Gain of catalytic residue at L516 (P = 0.0316);.;
MVP		0.043
MPC		0.041
ClinPred		0.17	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.064

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

LitVar

Other links and lift over

dbSNP: rs145455204; hg19: chr19-49933928; COSMIC: COSV55546441; COSMIC: COSV55546441;