17-18969052-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

1
18
Splicing: ADA: 0.00005607
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SLC5A10NM_001042450.4 linkc.454C>A p.Leu152Met missense_variant, splice_region_variant Exon 6 of 15 ENST00000395645.4 NP_001035915.1 A0PJK1-1
FAM83GNM_001039999.3 linkc.*2307G>T 3_prime_UTR_variant Exon 6 of 6 ENST00000388995.11 NP_001035088.2 A6ND36-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC5A10ENST00000395645.4 linkc.454C>A p.Leu152Met missense_variant, splice_region_variant Exon 6 of 15 1 NM_001042450.4 ENSP00000379007.3 A0PJK1-1
FAM83GENST00000388995 linkc.*2307G>T 3_prime_UTR_variant Exon 6 of 6 5 NM_001039999.3 ENSP00000373647.5 A6ND36-1

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
show subpopulations
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
LINK: link

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; API