rs147697689

Variant names:

• chr16-31490130-G-A
• rs147697689
• NM_003041.4:c.1692G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-31490130-G-A
• chr16-31490130-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_003041.4(SLC5A2):​c.1692G>A​(p.Arg564Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,614,076 control chromosomes in the GnomAD database, including 1 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 0.00062 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00093 (1 hom.)
• Consequence: SLC5A2 NM_003041.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.06

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 16-31490130-G-A is Benign according to our data. Variant chr16-31490130-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 319071.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A2	NM_003041.4	c.1692G>A	p.Arg564Arg	synonymous_variant	Exon 13 of 14	ENST00000330498.4	NP_003032.1
RUSF1	NM_022744.4	c.*705C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000327237.7	NP_073581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A2	ENST00000330498.4	c.1692G>A	p.Arg564Arg	synonymous_variant	Exon 13 of 14	1	NM_003041.4	ENSP00000327943.3
RUSF1	ENST00000327237	c.*705C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_022744.4	ENSP00000317579.2

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000737 AC: 185 AN: 251040 Hom.: 0 AF XY: 0.000700 AC XY: 95 AN XY: 135788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000928 AC: 1357 AN: 1461766 Hom.: 1 Cov.: 31 AF XY: 0.000847 AC XY: 616 AN XY: 727194

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.000689

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000937

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.000762

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40 AN XY: 74474

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000838 Hom.: 0

Bravo AF: 0.000646

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000771

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Familial renal glucosuria Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC5A2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

LitVar

Other links and lift over

dbSNP: rs147697689; hg19: chr16-31501451;