16-31484350-G-C

Variant names:

• chr16-31484350-G-C
• rs11646054
• NM_003041.4:c.127-323G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003041.4(SLC5A2):​c.127-323G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,188 control chromosomes in the GnomAD database, including 10,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (10299 hom., cov: 28)
• Consequence: SLC5A2 NM_003041.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 10 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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-31484350-G-C is Benign according to our data. Variant chr16-31484350-G-C is described in ClinVar as Benign. ClinVar VariationId is 1241803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

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.127-323G>C		intron	N/A	NP_003032.1	P31639-1
	SLC5A2	NR_130783.2		n.141-323G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.127-323G>C		intron	N/A	ENSP00000327943.3	P31639-1
	SLC5A2	ENST00000419665.6	TSL:1	n.127-323G>C		intron	N/A	ENSP00000410601.2	P31639-2
	SLC5A2	ENST00000865380.1		c.127-323G>C		intron	N/A	ENSP00000535439.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50532 AN: 151070 Hom.: 10294 Cov.: 28

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.334 AC: 50540 AN: 151188 Hom.: 10299 Cov.: 28 AF XY: 0.334 AC XY: 24646 AN XY: 73748

African (AFR) AF: 0.106 AC: 4365 AN: 41254

American (AMR) AF: 0.499 AC: 7585 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3466

East Asian (EAS) AF: 0.436 AC: 2246 AN: 5146

South Asian (SAS) AF: 0.188 AC: 901 AN: 4788

European-Finnish (FIN) AF: 0.361 AC: 3719 AN: 10314

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28775 AN: 67736

Other (OTH) AF: 0.408 AC: 855 AN: 2094

Alfa AF: 0.236 Hom.: 614

Bravo AF: 0.343

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.52
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11646054; hg19: chr16-31495671; COSMIC: COSV57893572; COSMIC: COSV57893572;