rs55698160

chr17-6694161-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_177550.5(SLC13A5):c.1092C>T(p.Ala364=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.141

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SLC13A5	NM_177550.5	c.1092C>T	p.Ala364=	synonymous_variant	8/12	ENST00000433363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A5	ENST00000433363.7	c.1092C>T	p.Ala364=	synonymous_variant	8/12	1	NM_177550.5	P1

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13659 AN: 152090 Hom.: 674 Cov.: 32

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

GnomAD3 exomes AF: 0.0691 AC: 17271 AN: 249990 Hom.: 714 AF XY: 0.0682 AC XY: 9216 AN XY: 135224

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 SAS exome AF: 0.0428

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.: 30 AF XY: 0.0850 AC XY: 61721 AN XY: 726452

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0398

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.0102

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.0960

Gnomad4 OTH exome AF: 0.0834

GnomAD4 genome AF: 0.0898 AC: 13670 AN: 152208 Hom.: 676 Cov.: 32 AF XY: 0.0861 AC XY: 6405 AN XY: 74430

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0848

Gnomad4 NFE AF: 0.0951

Gnomad4 OTH AF: 0.0780

Alfa AF: 0.0862 Hom.: 369

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 25 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.8
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs55698160; hg19: chr17-6597480; COSMIC: COSV53425091; COSMIC: COSV53425091;