rs55698160

Variant names:

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.1092C>T(p.Ala364Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,612,512 control chromosomes in the GnomAD database, including 6,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 676 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6046 hom. )

Consequence

SLC13A5
NM_177550.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.141

Publications

10 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=-0.68).

BP6

Variant 17-6694161-G-A is Benign according to our data. Variant chr17-6694161-G-A is described in ClinVar as Benign. ClinVar VariationId is 380900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.141 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5 link	c.1092C>T	p.Ala364Ala	synonymous_variant	Exon 8 of 12	ENST00000433363.7	NP_808218.1	Q86YT5-1Q68D44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7 link	c.1092C>T	p.Ala364Ala	synonymous_variant	Exon 8 of 12	1	NM_177550.5	ENSP00000406220.2		Q86YT5-1

Frequencies

GnomAD3 genomes

AF:

0.0898

AC:

13659

AN:

152090

Hom.:

674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0630

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00365

Gnomad SAS

AF:

0.0461

Gnomad FIN

AF:

0.0848

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0951

Gnomad OTH

AF:

0.0793

GnomAD2 exomes

AF:

0.0691

AC:

17271

AN:

249990

AF XY:

0.0682

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0372

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00578

Gnomad FIN exome

AF:

0.0846

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.0660

GnomAD4 exome

AF:

0.0868

AC:

126702

AN:

1460304

Hom.:

6046

Cov.:

AF XY:

0.0850

AC XY:

61721

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.117

AC:

3914

AN:

33378

American (AMR)

AF:

0.0398

AC:

1775

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

373

AN:

26126

East Asian (EAS)

AF:

0.0102

AC:

403

AN:

39662

South Asian (SAS)

AF:

0.0420

AC:

3614

AN:

86086

European-Finnish (FIN)

AF:

0.0893

AC:

4762

AN:

53350

Middle Eastern (MID)

AF:

0.0234

AC:

135

AN:

5768

European-Non Finnish (NFE)

AF:

0.0960

AC:

106693

AN:

1110936

Other (OTH)

AF:

0.0834

AC:

5033

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

4938

9876

14814

19752

24690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3816

7632

11448

15264

19080

<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:

0.0898

AC:

13670

AN:

152208

Hom.:

676

Cov.:

AF XY:

0.0861

AC XY:

6405

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.117

AC:

4844

AN:

41522

American (AMR)

AF:

0.0628

AC:

961

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.00366

AC:

AN:

5188

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4830

European-Finnish (FIN)

AF:

0.0848

AC:

899

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0951

AC:

6468

AN:

67984

Other (OTH)

AF:

0.0780

AC:

165

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

644

1288

1933

2577

3221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0853

Hom.:

574

Bravo

AF:

0.0878

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

EpiCase

AF:

0.0820

EpiControl

AF:

0.0798

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 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

-0.68

CADD

Benign

7.8

(source)

DANN

Benign

0.56

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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