16-31483196-T-C

Variant names:

• chr16-31483196-T-C
• rs114050461
• NM_003041.4:c.60T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0310
• Publications: 2 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 -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

Sel.	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.: 17 Cov.: 32

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

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.: 7 Cov.: 32 AF XY: 0.000481 AC XY: 350 AN XY: 727182

African (AFR) AF: 0.0225 AC: 754 AN: 33480

American (AMR) AF: 0.00114 AC: 51 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111992

Other (OTH) AF: 0.00124 AC: 75 AN: 60392

GnomAD4 genome AF: 0.00640 AC: 974 AN: 152232 Hom.: 17 Cov.: 32 AF XY: 0.00590 AC XY: 439 AN XY: 74418

African (AFR) AF: 0.0225 AC: 934 AN: 41540

American (AMR) AF: 0.00157 AC: 24 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00427 AC: 9 AN: 2106

Alfa AF: 0.00317 Hom.: 1

Bravo AF: 0.00696

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial renal glucosuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.51
DANN	Benign	0.47
PhyloP100		-0.031
PromoterAI		0.084	Neutral
Mutation Taster		=100/0	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: rs114050461; hg19: chr16-31494517;