chr16-31490130-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.24).
• 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 VariationId is 319071.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.

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.1692G>A	p.Arg564Arg	synonymous	Exon 13 of 14	NP_003032.1	P31639-1
	RUSF1	NM_022744.4	MANE Select	c.*705C>T		3_prime_UTR	Exon 13 of 13	NP_073581.2	Q96GQ5-1
	SLC5A2	NR_130783.2		n.1386G>A		non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.1692G>A	p.Arg564Arg	synonymous	Exon 13 of 14	ENSP00000327943.3	P31639-1
	RUSF1	ENST00000327237.7	TSL:1 MANE Select	c.*705C>T		3_prime_UTR	Exon 13 of 13	ENSP00000317579.2	Q96GQ5-1
	SLC5A2	ENST00000419665.6	TSL:1	n.1372G>A		non_coding_transcript_exon	Exon 11 of 12	ENSP00000410601.2	P31639-2

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

GnomAD2 exomes AF: 0.000737 AC: 185 AN: 251040 AF XY: 0.000700

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 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

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00114 AC: 1266 AN: 1112004

Other (OTH) AF: 0.000762 AC: 46 AN: 60390

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

African (AFR) AF: 0.000144 AC: 6 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

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

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Familial renal glucosuria (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs147697689; hg19: chr16-31501451;