chr17-6703699-G-A

Variant names:

• chr17-6703699-G-A
• rs218676
• NM_177550.5:c.547+179C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177550.5(SLC13A5):​c.547+179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,076 control chromosomes in the GnomAD database, including 5,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5390 hom., cov: 32)
• Consequence: SLC13A5 NM_177550.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-6703699-G-A is Benign according to our data. Variant chr17-6703699-G-A is described in ClinVar as Benign. ClinVar VariationId is 670096.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5	c.547+179C>T		intron_variant	Intron 4 of 11	ENST00000433363.7	NP_808218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7	c.547+179C>T		intron_variant	Intron 4 of 11	1	NM_177550.5	ENSP00000406220.2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37745 AN: 151960 Hom.: 5397 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37740 AN: 152076 Hom.: 5390 Cov.: 32 AF XY: 0.252 AC XY: 18699 AN XY: 74342

African (AFR) AF: 0.321 AC: 13314 AN: 41476

American (AMR) AF: 0.268 AC: 4096 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3042 AN: 5170

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10566

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.184 AC: 12497 AN: 67982

Other (OTH) AF: 0.258 AC: 544 AN: 2106

Alfa AF: 0.207 Hom.: 13326

Bravo AF: 0.258

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

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.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.36
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs218676; hg19: chr17-6607018;