rs56224509

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_177550.5(SLC13A5):c.1005C>T(p.Pro335Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 1,614,094 control chromosomes in the GnomAD database, including 6,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P335P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.065 ( 394 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5667 hom. )

Consequence

SLC13A5
NM_177550.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.94

Publications

9 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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 25
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
amelocerebrohypohidrotic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pyridoxine-dependent epilepsy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC13A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 17-6695776-G-A is Benign according to our data. Variant chr17-6695776-G-A is described in ClinVar as Benign. ClinVar VariationId is 380899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5 link	c.1005C>T	p.Pro335Pro	synonymous_variant	Exon 7 of 12	ENST00000433363.7	NP_808218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7 link	c.1005C>T	p.Pro335Pro	synonymous_variant	Exon 7 of 12	1	NM_177550.5	ENSP00000406220.2

Frequencies

GnomAD3 genomes

AF:

0.0652

AC:

9923

AN:

152098

Hom.:

394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0390

Gnomad FIN

AF:

0.0849

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0937

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0615

AC:

15458

AN:

251296

AF XY:

0.0617

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.0328

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00359

Gnomad FIN exome

AF:

0.0845

Gnomad NFE exome

AF:

0.0903

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

AF:

0.0833

AC:

121810

AN:

1461878

Hom.:

5667

Cov.:

AF XY:

0.0818

AC XY:

59457

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0295

AC:

988

AN:

33480

American (AMR)

AF:

0.0340

AC:

1521

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

359

AN:

26136

East Asian (EAS)

AF:

0.00758

AC:

301

AN:

39700

South Asian (SAS)

AF:

0.0370

AC:

3194

AN:

86258

European-Finnish (FIN)

AF:

0.0891

AC:

4760

AN:

53414

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0953

AC:

105989

AN:

1112004

Other (OTH)

AF:

0.0765

AC:

4620

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6807

13613

20420

27226

34033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3754

7508

11262

15016

18770

<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

AF:

0.0652

AC:

9924

AN:

152216

Hom.:

394

Cov.:

AF XY:

0.0626

AC XY:

4662

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0350

AC:

1452

AN:

41544

American (AMR)

AF:

0.0516

AC:

790

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4822

European-Finnish (FIN)

AF:

0.0849

AC:

900

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0937

AC:

6373

AN:

67988

Other (OTH)

AF:

0.0592

AC:

125

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

477

954

1431

1908

2385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0663

Hom.:

340

Bravo

AF:

0.0593

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

EpiCase

AF:

0.0808

EpiControl

AF:

0.0775

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 25

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 12, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases

Benign:1

Apr 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.68

(source)

DANN

Benign

0.76

PhyloP100

-4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over