17-18952242-G-A

Variant names:

• chr17-18952242-G-A
• rs757159430
• NM_001042450.4:c.37G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042450.4(SLC5A10):​c.37G>A​(p.Gly13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SLC5A10 NM_001042450.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.43

Genes affected

SLC5A10 (HGNC:23155): (solute carrier family 5 member 10) This gene is a member of the sodium/glucose transporter family. Members of this family are sodium-dependent transporters and can be divided into two subfamilies based on sequence homology, one that co-transports sugars and the second that transports molecules such as ascorbate, choline, iodide, lipoate, monocaroboxylates, and pantothenate. The protein encoded by this gene has the highest affinity for mannose and has been reported to be most highly expressed in the kidney. This protein may function as a kidney-specific, sodium-dependent mannose and fructose co-transporter. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ENSG00000196893 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040254384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A10	NM_001042450.4	c.37G>A	p.Gly13Arg	missense_variant	Exon 1 of 15	ENST00000395645.4	NP_001035915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A10	ENST00000395645.4	c.37G>A	p.Gly13Arg	missense_variant	Exon 1 of 15	1	NM_001042450.4	ENSP00000379007.3

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000282 AC: 7 AN: 248066 Hom.: 0 AF XY: 0.0000297 AC XY: 4 AN XY: 134728

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461534 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10 AN XY: 727036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37G>A (p.G13R) alteration is located in exon 1 (coding exon 1) of the SLC5A10 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the glycine (G) at amino acid position 13 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.76
DANN	Benign	0.70
DEOGEN2	Benign	0.011	.;.;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.79	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.35	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.097
MutPred		0.28		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.12
MPC		0.25
ClinPred		0.024	T
GERP RS		-2.5
Varity_R		0.029
gMVP		0.54

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: rs757159430; hg19: chr17-18855555;