Variant 19-49430529-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_020309.4(SLC17A7):c.1673G>A(p.Arg558Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,570,730 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 22 hom. )

Consequence

SLC17A7
NM_020309.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.77

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]

SLC17A7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, SLC17A7

BP4

Computational evidence support a benign effect (MetaRNN=0.005351007).

BP6

Variant 19-49430529-C-T is Benign according to our data. Variant chr19-49430529-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650241.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A7	NM_020309.4 linkuse as main transcript	c.1673G>A	p.Arg558Gln	missense_variant	12/12	ENST00000221485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A7	ENST00000221485.8 linkuse as main transcript	c.1673G>A	p.Arg558Gln	missense_variant	12/12	1	NM_020309.4	P1	Q9P2U7-1
SLC17A7	ENST00000600601.5 linkuse as main transcript	c.1472G>A	p.Arg491Gln	missense_variant	12/12	2			Q9P2U7-2

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

312

AN:

147166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000546

Gnomad ASJ

AF:

0.0183

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00943

Gnomad FIN

AF:

0.000407

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00298

GnomAD3 exomes

AF:

0.00305

AC:

656

AN:

215340

Hom.:

AF XY:

0.00362

AC XY:

417

AN XY:

115084

show subpopulations

Gnomad AFR exome

AF:

0.000407

Gnomad AMR exome

AF:

0.000757

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00982

Gnomad FIN exome

AF:

0.000159

Gnomad NFE exome

AF:

0.00276

Gnomad OTH exome

AF:

0.00437

GnomAD4 exome

AF:

0.00287

AC:

4080

AN:

1423480

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

2207

AN XY:

703578

show subpopulations

Gnomad4 AFR exome

AF:

0.000365

Gnomad4 AMR exome

AF:

0.000812

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0106

Gnomad4 FIN exome

AF:

0.000369

Gnomad4 NFE exome

AF:

0.00239

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00210

AC:

309

AN:

147250

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

141

AN XY:

71684

show subpopulations

Gnomad4 AFR

AF:

0.000380

Gnomad4 AMR

AF:

0.000545

Gnomad4 ASJ

AF:

0.0183

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00925

Gnomad4 FIN

AF:

0.000407

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00246

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00183

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00281

AC:

341

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SLC17A7: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.87

D;D

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.73

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.32

N;.

REVEL

Benign

0.12

Sift

Uncertain

0.020

D;.

Sift4G

Benign

0.097

T;T

Polyphen

0.83

P;.

Vest4

0.10

MVP

0.082

MPC

0.19

ClinPred

0.040

GERP RS

4.7

Varity_R

0.15

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over