dbSNP rs114050461: SLC5A2:p.Ile20Ile (chr16-31483196-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003041.4(SLC5A2):c.60T>C(p.Ile20Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,614,016 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 7 hom. )

Consequence

SLC5A2
NM_003041.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0310

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 Gene-Disease associations (from GenCC):

familial renal glucosuria
Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Orphanet

SLC5A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 16-31483196-T-C is Benign according to our data. Variant chr16-31483196-T-C is described in ClinVar as Benign. ClinVar VariationId is 777013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.031 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0064 (974/152232) while in subpopulation AFR AF = 0.0225 (934/41540). AF 95% confidence interval is 0.0213. There are 17 homozygotes in GnomAd4. There are 439 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A2	NM_003041.4	MANE Select	c.60T>C	p.Ile20Ile	synonymous	Exon 1 of 14	NP_003032.1	P31639-1
	SLC5A2	NR_130783.2		n.74T>C		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.60T>C	p.Ile20Ile	synonymous	Exon 1 of 14	ENSP00000327943.3	P31639-1
SLC5A2	ENST00000419665.6	TSL:1	n.60T>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000410601.2	P31639-2
SLC5A2	ENST00000865380.1		c.60T>C	p.Ile20Ile	synonymous	Exon 1 of 14	ENSP00000535439.1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

973

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00432

GnomAD2 exomes

AF:

0.00168

AC:

423

AN:

251380

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000610

AC:

891

AN:

1461784

Hom.:

Cov.:

AF XY:

0.000481

AC XY:

350

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.0225

AC:

754

AN:

33480

American (AMR)

AF:

0.00114

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111992

Other (OTH)

AF:

0.00124

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00640

AC:

974

AN:

152232

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0225

AC:

934

AN:

41540

American (AMR)

AF:

0.00157

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68026

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

149

198

248

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:

0.00317

Hom.:

Bravo

AF:

0.00696

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial renal glucosuria (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.51

(source)

DANN

Benign

0.47

PhyloP100

-0.031

PromoterAI

0.084

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over