Genetic Variant SLC5A2:p.Arg558Leu (chr16-31490111-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_003041.4(SLC5A2):c.1673G>T(p.Arg558Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R558H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SLC5A2
NM_003041.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.18

Publications

2 publications found

Variant links:

Genes affected

SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

SLC5A2 links:

RUSF1 (HGNC:25848): (RUS family member 1) This gene encodes a putative transmembrane protein containing a conserved DUF647 domain that may be involved in protein-protein interaction. The encoded protein is related to a plant protein that participates in ultraviolet B light-sensing during root morphogenesis. [provided by RefSeq, Feb 2013]

RUSF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003041.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A2	NM_003041.4	MANE Select	c.1673G>T	p.Arg558Leu	missense	Exon 13 of 14	NP_003032.1	P31639-1
RUSF1	NM_022744.4	MANE Select	c.*724C>A		3_prime_UTR	Exon 13 of 13	NP_073581.2	Q96GQ5-1
SLC5A2	NR_130783.2		n.1367G>T		non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.1673G>T	p.Arg558Leu	missense	Exon 13 of 14	ENSP00000327943.3	P31639-1
RUSF1	ENST00000327237.7	TSL:1 MANE Select	c.*724C>A		3_prime_UTR	Exon 13 of 13	ENSP00000317579.2	Q96GQ5-1
SLC5A2	ENST00000419665.6	TSL:1	n.1353G>T		non_coding_transcript_exon	Exon 11 of 12	ENSP00000410601.2	P31639-2

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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.38

MetaRNN

Pathogenic

0.81

MetaSVM

Uncertain

-0.019

MutationAssessor

Uncertain

2.7

PhyloP100

7.2

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.055

Polyphen

0.38

Vest4

0.63

MutPred

0.68

Gain of sheet (P = 0.0166)

MVP

0.96

MPC

0.41

ClinPred

0.98

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.61

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 13

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

Publications

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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