Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003041.4(SLC5A2):c.1961A>G(p.Asn654Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00703 in 1,613,962 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 58 hom. )

Consequence

SLC5A2
NM_003041.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:5B:3

Conservation

PhyloP100: 6.19

Publications

29 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010311753).

BP6

Variant 16-31490477-A-G is Benign according to our data. Variant chr16-31490477-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 12905.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00514 (783/152298) while in subpopulation NFE AF = 0.00765 (520/68014). AF 95% confidence interval is 0.0071. There are 7 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

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
SLC5A2	NM_003041.4	MANE Select	c.1961A>G	p.Asn654Ser	missense	Exon 14 of 14	NP_003032.1
RUSF1	NM_022744.4	MANE Select	c.*358T>C		3_prime_UTR	Exon 13 of 13	NP_073581.2
SLC5A2	NR_130783.2		n.1655A>G		non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.1961A>G	p.Asn654Ser	missense	Exon 14 of 14	ENSP00000327943.3
SLC5A2	ENST00000419665.6	TSL:1	n.*264A>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000410601.2
RUSF1	ENST00000327237.7	TSL:1 MANE Select	c.*358T>C		3_prime_UTR	Exon 13 of 13	ENSP00000317579.2

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

783

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00764

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00560

AC:

1391

AN:

248370

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.000743

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.0302

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00155

Gnomad NFE exome

AF:

0.00824

Gnomad OTH exome

AF:

0.00756

GnomAD4 exome

AF:

0.00722

AC:

10556

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00693

AC XY:

5042

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33476

American (AMR)

AF:

0.00295

AC:

132

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0306

AC:

799

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00182

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00815

AC:

9061

AN:

1111964

Other (OTH)

AF:

0.00715

AC:

432

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

660

1319

1979

2638

3298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00514

AC:

783

AN:

152298

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

368

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

41560

American (AMR)

AF:

0.00386

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00765

AC:

520

AN:

68014

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00827

Hom.:

Bravo

AF:

0.00584

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00228

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00523

AC:

635

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00836

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial renal glucosuria (5)

not provided (2)

not specified (1)

SLC5A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

3.4

PhyloP100

6.2

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.2

REVEL

Pathogenic

0.67

Sift

Benign

0.050

Sift4G

Uncertain

0.031

Polyphen

0.88

Vest4

0.27

MVP

0.98

MPC

0.49

ClinPred

0.079

GERP RS

5.3

Varity_R

0.28

gMVP

0.72

Mutation Taster

=89/11

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

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rs61742739

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over