17-18969052-C-A

Variant names:

• chr17-18969052-C-A
• NM_001042450.4:c.454C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042450.4(SLC5A10):​c.454C>A​(p.Leu152Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC5A10 NM_001042450.4 missense, splice_region
• Scores: Splicing: ADA: 0.00005607
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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]

FAM83G (HGNC:32554): (family with sequence similarity 83 member G) Predicted to enable protein kinase binding activity. Involved in BMP signaling pathway. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21239468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A10	NM_001042450.4	c.454C>A	p.Leu152Met	missense_variant, splice_region_variant	Exon 6 of 15	ENST00000395645.4	NP_001035915.1
FAM83G	NM_001039999.3	c.*2307G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000388995.11	NP_001035088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A10	ENST00000395645.4	c.454C>A	p.Leu152Met	missense_variant, splice_region_variant	Exon 6 of 15	1	NM_001042450.4	ENSP00000379007.3
FAM83G	ENST00000388995	c.*2307G>T		3_prime_UTR_variant	Exon 6 of 6	5	NM_001039999.3	ENSP00000373647.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460422 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.454C>A (p.L152M) alteration is located in exon 6 (coding exon 6) of the SLC5A10 gene. This alteration results from a C to A substitution at nucleotide position 454, causing the leucine (L) at amino acid position 152 to be replaced by a methionine (M). 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	0.099
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.033	.;.;.;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.71	T;T;T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.55	.;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.33	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.090	T;T;T;T;T
Sift4G	Benign	0.067	T;T;T;T;T
Polyphen		0.71	P;P;.;B;B
Vest4		0.29
MutPred		0.41		.;Loss of ubiquitination at K149 (P = 0.0787);Loss of ubiquitination at K149 (P = 0.0787);Loss of ubiquitination at K149 (P = 0.0787);Loss of ubiquitination at K149 (P = 0.0787);
MVP		0.32
MPC		0.24
ClinPred		0.26	T
GERP RS		-2.2
Varity_R		0.060
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.020
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18872365;