dbSNP rs569395560: SLC13A5:p.Thr528Ser (chr17-6686332-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177550.5(SLC13A5):c.1582A>T(p.Thr528Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T528A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC13A5
NM_177550.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278

Publications

0 publications found

Variant links:

Genes affected

SLC13A5 (HGNC:23089): (solute carrier family 13 member 5) This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

SLC13A5 links:

ENSG00000290366 (HGNC:):

ENSG00000290366 links:

C17orf100 (HGNC:34494): (chromosome 17 open reading frame 100)

C17orf100 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.20337185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLC13A5	NM_177550.5 link	c.1582A>T	p.Thr528Ser	missense_variant	Exon 12 of 12	ENST00000433363.7	NP_808218.1
SLC13A5	NM_001284509.2 link	c.1531A>T	p.Thr511Ser	missense_variant	Exon 12 of 12		NP_001271438.1
SLC13A5	NM_001284510.2 link	c.1453A>T	p.Thr485Ser	missense_variant	Exon 11 of 11		NP_001271439.1
SLC13A5	NM_001143838.3 link	c.1444A>T	p.Thr482Ser	missense_variant	Exon 11 of 11		NP_001137310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7 link	c.1582A>T	p.Thr528Ser	missense_variant	Exon 12 of 12	1	NM_177550.5	ENSP00000406220.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;.;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

L;.;.;.

PhyloP100

-0.28

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

.;.;N;.

REVEL

Benign

0.057

Sift

Benign

0.13

.;.;T;.

Sift4G

Benign

0.093

T;T;T;T

Polyphen

0.16

B;.;.;.

Vest4

0.050

MutPred

0.69

Gain of glycosylation at T528 (P = 0.0758);.;.;.;

MVP

0.28

MPC

0.26

ClinPred

0.26

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.63

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over