rs56224509

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000433363.7(SLC13A5):c.1005C>T(p.Pro335=) 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
ENST00000433363.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SLC13A5	NM_177550.5 linkuse as main transcript	c.1005C>T	p.Pro335=	synonymous_variant	7/12	ENST00000433363.7	NP_808218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7 linkuse as main transcript	c.1005C>T	p.Pro335=	synonymous_variant	7/12	1	NM_177550.5	ENSP00000406220	P1	Q86YT5-1

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

GnomAD3 exomes

AF:

0.0615

AC:

15458

AN:

251296

Hom.:

613

AF XY:

0.0617

AC XY:

8387

AN XY:

135830

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 SAS exome

AF:

0.0371

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

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.00758

Gnomad4 SAS exome

AF:

0.0370

Gnomad4 FIN exome

AF:

0.0891

Gnomad4 NFE exome

AF:

0.0953

Gnomad4 OTH exome

AF:

0.0765

GnomAD4 genome

AF:

0.0652

AC:

9924

AN:

152216

Hom.:

394

Cov.:

AF XY:

0.0626

AC XY:

4662

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.0516

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0392

Gnomad4 FIN

AF:

0.0849

Gnomad4 NFE

AF:

0.0937

Gnomad4 OTH

AF:

0.0592

Alfa

AF:

0.0646

Hom.:

197

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

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Developmental and epileptic encephalopathy, 25

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2016

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2016

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

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over