rs1378076282

Variant names:

• chr16-31485841-G-A
• rs1378076282
• NM_003041.4:c.416G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-31485841-G-A
• chr16-31485841-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

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
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 9 uncertain in NM_003041.4

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.416G>A	p.Arg139His	missense	Exon 4 of 14	NP_003032.1	P31639-1
	SLC5A2	NR_130783.2		n.430G>A		non_coding_transcript_exon	Exon 4 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.416G>A	p.Arg139His	missense	Exon 4 of 14	ENSP00000327943.3	P31639-1
	SLC5A2	ENST00000419665.6	TSL:1	n.416G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000410601.2	P31639-2
	SLC5A2	ENST00000865380.1		c.404G>A	p.Arg135His	missense	Exon 4 of 14	ENSP00000535439.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250774 AF XY: 0.00000737

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Familial renal glucosuria (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Benign	1.7	L
PhyloP100		2.1
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.54
Sift	Benign	0.066	T
Sift4G	Uncertain	0.041	D
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
Mutation Taster		=83/17	polymorphism

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