16-31484724-C-G

Variant names:

• chr16-31484724-C-G
• rs201586410
• NM_003041.4:c.178C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003041.4(SLC5A2):​c.178C>G​(p.Arg60Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,338 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC5A2 NM_003041.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A2	NM_003041.4	c.178C>G	p.Arg60Gly	missense_variant	Exon 2 of 14	ENST00000330498.4	NP_003032.1
SLC5A2	XM_006721072.5	c.178C>G	p.Arg60Gly	missense_variant	Exon 2 of 13		XP_006721135.3
SLC5A2	XM_024450402.2	c.178C>G	p.Arg60Gly	missense_variant	Exon 2 of 11		XP_024306170.2
SLC5A2	NR_130783.2	n.192C>G		non_coding_transcript_exon_variant	Exon 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A2	ENST00000330498.4	c.178C>G	p.Arg60Gly	missense_variant	Exon 2 of 14	1	NM_003041.4	ENSP00000327943.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74492

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.63	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.63
Sift	Benign	0.086	T;T
Sift4G	Benign	0.11	T;T
Polyphen		1.0	.;D
Vest4		0.69
MVP		0.95
MPC		0.93
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.75
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: 20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201586410; hg19: chr16-31496045; COSMIC: COSV100393412; COSMIC: COSV100393412;