6-25761999-G-T

Position:

chr6-25761999-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005495.3(SLC17A4):c.37G>T(p.Asp13Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000523 in 1,613,886 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 2 hom. )

Consequence

SLC17A4
NM_005495.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.480

Variant links:

Genes affected

SLC17A4 (HGNC:10932): (solute carrier family 17 member 4) Phosphate homeostasis is maintained by regulating intake, intestinal absorption, bone deposition and resorption, and renal excretion of phosphate. The central molecule in the control of phosphate excretion from the kidney is the sodium/phosphate cotransporter NPT1 (SLC17A1; MIM 182308), which is located in the renal proximal tubule. NPT1 uses the transmembrane electrochemical potential gradient of sodium to transport phosphate across the cell membrane. SLC17A4 is a similar sodium/phosphate cotransporter in the intestinal mucosa that plays an important role in the absorption of phosphate from the intestine (summary by Shibui et al., 1999 [PubMed 10319585]).[supplied by OMIM, Feb 2011]

SLC17A4 links:

SLC17A1 (HGNC:):

SLC17A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01386109).

BP6

Variant 6-25761999-G-T is Benign according to our data. Variant chr6-25761999-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2352092.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A4	NM_005495.3 linkuse as main transcript	c.37G>T	p.Asp13Tyr	missense_variant	2/12	ENST00000377905.9	NP_005486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A4	ENST00000377905.9 linkuse as main transcript	c.37G>T	p.Asp13Tyr	missense_variant	2/12	1	NM_005495.3	ENSP00000367137	P1	Q9Y2C5-1
SLC17A4	ENST00000397076.2 linkuse as main transcript	c.-226G>T		5_prime_UTR_variant	1/7	2		ENSP00000380266		Q9Y2C5-4
SLC17A4	ENST00000439485.6 linkuse as main transcript	c.-226G>T		5_prime_UTR_variant	2/13	5		ENSP00000391345		Q9Y2C5-2

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000494

AC:

124

AN:

251056

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000555

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000519

AC:

758

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000527

AC XY:

383

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000492

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.000565

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.000895

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.00101

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.37G>T (p.D13Y) alteration is located in exon 2 (coding exon 1) of the SLC17A4 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the aspartic acid (D) at amino acid position 13 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SLC17A4: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.15

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.49

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.23

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.016

Polyphen

0.96

Vest4

0.21

MVP

0.38

MPC

0.14

ClinPred

0.068

GERP RS

-0.91

Varity_R

0.097

gMVP

0.43

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