NM_003041.4:c.1807G>A

Variant names:

• chr16-31490323-G-A
• rs1188721313
• NM_003041.4:c.1807G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003041.4(SLC5A2):​c.1807G>A​(p.Ala603Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC5A2 NM_003041.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0510
• Publications: 0 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]

RUSF1 (HGNC:25848): (RUS family member 1) This gene encodes a putative transmembrane protein containing a conserved DUF647 domain that may be involved in protein-protein interaction. The encoded protein is related to a plant protein that participates in ultraviolet B light-sensing during root morphogenesis. [provided by RefSeq, Feb 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09654227).

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.1807G>A	p.Ala603Thr	missense	Exon 14 of 14	NP_003032.1	P31639-1
	RUSF1	NM_022744.4	MANE Select	c.*512C>T		3_prime_UTR	Exon 13 of 13	NP_073581.2	Q96GQ5-1
	SLC5A2	NR_130783.2		n.1501G>A		non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A2	ENST00000330498.4	TSL:1 MANE Select	c.1807G>A	p.Ala603Thr	missense	Exon 14 of 14	ENSP00000327943.3	P31639-1
	RUSF1	ENST00000327237.7	TSL:1 MANE Select	c.*512C>T		3_prime_UTR	Exon 13 of 13	ENSP00000317579.2	Q96GQ5-1
	SLC5A2	ENST00000419665.6	TSL:1	n.*110G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000410601.2	P31639-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243390 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.000169

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726030

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111262

Other (OTH) AF: 0.0000166 AC: 1 AN: 60288

GnomAD4 genome Cov.: 33

Alfa AF: 0.000111 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Familial renal glucosuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.0
DANN	Benign	0.52
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.22	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.76	N
PhyloP100		0.051
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.14
Sift	Benign	0.53	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.15		Gain of phosphorylation at A603 (P = 0.0302)
MVP		0.54
MPC		0.22
ClinPred		0.025	T
GERP RS		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.028
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1188721313; hg19: chr16-31501644;