Variant 6-25769173-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005495.3(SLC17A4):c.280A>G(p.Lys94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC17A4
NM_005495.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.621

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06798288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A4	NM_005495.3 linkuse as main transcript	c.280A>G	p.Lys94Glu	missense_variant	3/12	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.280A>G	p.Lys94Glu	missense_variant	3/12	1	NM_005495.3	ENSP00000367137	P1	Q9Y2C5-1
SLC17A4	ENST00000439485.6 linkuse as main transcript	c.118A>G	p.Lys40Glu	missense_variant	4/13	5		ENSP00000391345		Q9Y2C5-2
SLC17A4	ENST00000397076.2 linkuse as main transcript	c.118A>G	p.Lys40Glu	missense_variant	3/7	2		ENSP00000380266		Q9Y2C5-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Nov 30, 2022

The c.280A>G (p.K94E) alteration is located in exon 3 (coding exon 2) of the SLC17A4 gene. This alteration results from a A to G substitution at nucleotide position 280, causing the lysine (K) at amino acid position 94 to be replaced by a glutamic acid (E). 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

Benign

0.063

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.7

DANN

Benign

0.61

DEOGEN2

Benign

0.073

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

.;N;N

REVEL

Benign

0.13

Sift

Benign

0.21

.;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.10

MutPred

0.56

.;Loss of ubiquitination at K94 (P = 0.013);.;

MVP

0.21

MPC

0.10

ClinPred

0.32

GERP RS

-8.8

Varity_R

0.088

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over