NM_003041.4:c.2T>G

Variant names:

• chr16-31483138-T-G
• rs780546914
• NM_003041.4:c.2T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_003041.4(SLC5A2):​c.2T>G​(p.Met1?) variant causes a start lost 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC5A2 NM_003041.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

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 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 13 codons. Genomic position: 31483173. Lost 0.018 part of the original CDS.
• 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.2T>G	p.Met1?	start_lost	Exon 1 of 14	ENST00000330498.4	NP_003032.1
SLC5A2	XM_006721072.5	c.2T>G	p.Met1?	start_lost	Exon 1 of 13		XP_006721135.3
SLC5A2	XM_024450402.2	c.2T>G	p.Met1?	start_lost	Exon 1 of 11		XP_024306170.2
SLC5A2	NR_130783.2	n.16T>G		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A2	ENST00000330498.4	c.2T>G	p.Met1?	start_lost	Exon 1 of 14	1	NM_003041.4	ENSP00000327943.3
SLC5A2	ENST00000419665.6	n.2T>G		non_coding_transcript_exon_variant	Exon 1 of 12	1		ENSP00000410601.2
SLC5A2	ENST00000569576.5	c.-4+70T>G		intron_variant	Intron 1 of 4	4		ENSP00000455143.1
SLC5A2	ENST00000562006.1	n.1T>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.27	D
PROVEAN	Benign	-1.0	N
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.86	P
Vest4		0.90
MutPred		0.98		Loss of catalytic residue at M1 (P = 0.0424);
MVP		0.95
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.95
gMVP		0.84

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: rs780546914; hg19: chr16-31494459;