Genetic Variant SLC17A4:p.Lys490Asn (chr6-25779164-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005495.3(SLC17A4):c.1470A>T(p.Lys490Asn) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC17A4
NM_005495.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.382

Publications

17 publications found

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:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11723605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005495.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A4	NM_005495.3	MANE Select	c.1470A>T	p.Lys490Asn	missense	Exon 12 of 12	NP_005486.1	Q9Y2C5-1
	SLC17A4	NM_001286121.1		c.1308A>T	p.Lys436Asn	missense	Exon 13 of 13	NP_001273050.1	Q9Y2C5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A4	ENST00000377905.9	TSL:1 MANE Select	c.1470A>T	p.Lys490Asn	missense	Exon 12 of 12	ENSP00000367137.4	Q9Y2C5-1
SLC17A4	ENST00000867588.1		c.1470A>T	p.Lys490Asn	missense	Exon 12 of 12	ENSP00000537647.1
SLC17A4	ENST00000867590.1		c.1470A>T	p.Lys490Asn	missense	Exon 12 of 12	ENSP00000537649.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.071

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.057

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-0.38

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.025

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.012

Polyphen

0.11

Vest4

0.15

MutPred

0.40

Loss of methylation at K490 (P = 0.0078)

MVP

0.25

MPC

0.26

ClinPred

0.87

GERP RS

0.30

Varity_R

0.34

gMVP

0.26

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over