16-31484914-C-A

Position:

• chr16-31484914-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_003041.4(SLC5A2):​c.294C>A​(p.Phe98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC5A2 NM_003041.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.116

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811
• PP5: Variant 16-31484914-C-A is Pathogenic according to our data. Variant chr16-31484914-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 29882.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-31484914-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A2	NM_003041.4	c.294C>A	p.Phe98Leu	missense_variant	3/14	ENST00000330498.4
SLC5A2	XM_006721072.5	c.294C>A	p.Phe98Leu	missense_variant	3/13
SLC5A2	XM_024450402.2	c.294C>A	p.Phe98Leu	missense_variant	3/11
SLC5A2	NR_130783.2	n.308C>A		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A2	ENST00000330498.4	c.294C>A	p.Phe98Leu	missense_variant	3/14	1	NM_003041.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial renal glucosuria Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.83	T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.36	D
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.2	D;D
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.050	T;D
Polyphen		1.0	.;D
Vest4		0.94
MutPred		0.67		.;Gain of helix (P = 0.2294);
MVP		0.97
MPC		0.91
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.63
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.38		Position offset: 9

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

Publications

LitVar

Other links and lift over

dbSNP: rs398122802; hg19: chr16-31496235;