rs1378076282

Positions:

• chr16-31485841-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_003041.4(SLC5A2):​c.416G>A​(p.Arg139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SLC5A2 NM_003041.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A2	NM_003041.4	c.416G>A	p.Arg139His	missense_variant	4/14	ENST00000330498.4
SLC5A2	XM_006721072.5	c.416G>A	p.Arg139His	missense_variant	4/13
SLC5A2	XM_024450402.2	c.416G>A	p.Arg139His	missense_variant	4/11
SLC5A2	NR_130783.2	n.430G>A		non_coding_transcript_exon_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A2	ENST00000330498.4	c.416G>A	p.Arg139His	missense_variant	4/14	1	NM_003041.4	P1
SLC5A2	ENST00000419665.6	c.416G>A	p.Arg139His	missense_variant, NMD_transcript_variant	4/12	1
SLC5A2	ENST00000569576.5	c.287G>A	p.Arg96His	missense_variant	4/5	4
SLC5A2	ENST00000565446.1	n.290G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250774 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135660

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461090 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726926

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial renal glucosuria Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 03, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	May 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	0.57	D
MutationTaster	Benign	0.92	D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D;D
Sift	Benign	0.066	T;D
Sift4G	Uncertain	0.041	D;T
Polyphen		0.99	.;D
Vest4		0.50
MutPred		0.65		.;Loss of MoRF binding (P = 0.0139);
MVP		0.99
MPC		0.87
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs1378076282; hg19: chr16-31497162; COSMIC: COSV57894750; COSMIC: COSV57894750;