16-31490146-CG-C

Variant names:

• chr16-31490146-CG-C
• NM_003041.4:c.1711delG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_003041.4(SLC5A2):​c.1711delG​(p.Glu571ArgfsTer26) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC5A2 NM_003041.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.39
• 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-31490146-CG-C is Pathogenic according to our data. Variant chr16-31490146-CG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3580367.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1711delG	p.Glu571ArgfsTer26	frameshift	Exon 13 of 14	NP_003032.1	P31639-1
	RUSF1	NM_022744.4	MANE Select	c.*688delC		3_prime_UTR	Exon 13 of 13	NP_073581.2	Q96GQ5-1
	SLC5A2	NR_130783.2		n.1405delG		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.1711delG	p.Glu571ArgfsTer26	frameshift	Exon 13 of 14	ENSP00000327943.3	P31639-1
	RUSF1	ENST00000327237.7	TSL:1 MANE Select	c.*688delC		3_prime_UTR	Exon 13 of 13	ENSP00000317579.2	Q96GQ5-1
	SLC5A2	ENST00000419665.6	TSL:1	n.*14delG		non_coding_transcript_exon	Exon 11 of 12	ENSP00000410601.2	P31639-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Familial renal glucosuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4

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

hg19: chr16-31501467;