rs143719876

Variant names:

• chr17-6687657-T-C
• rs143719876
• NM_177550.5:c.1447A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_177550.5(SLC13A5):​c.1447A>G​(p.Ile483Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,603,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. I483I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.18
• Publications: 2 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]

ENSG00000290366 (HGNC:):

C17orf100 (HGNC:34494): (chromosome 17 open reading frame 100)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25616673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177550.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A5	NM_177550.5	MANE Select	c.1447A>G	p.Ile483Val	missense	Exon 11 of 12	NP_808218.1	Q86YT5-1
	SLC13A5	NM_001284509.2		c.1396A>G	p.Ile466Val	missense	Exon 11 of 12	NP_001271438.1	Q86YT5-3
	SLC13A5	NM_001284510.2		c.1318A>G	p.Ile440Val	missense	Exon 10 of 11	NP_001271439.1	Q86YT5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A5	ENST00000433363.7	TSL:1 MANE Select	c.1447A>G	p.Ile483Val	missense	Exon 11 of 12	ENSP00000406220.2	Q86YT5-1
	SLC13A5	ENST00000573648.5	TSL:1	c.1438-1319A>G		intron	N/A	ENSP00000459372.1	Q86YT5-2
	SLC13A5	ENST00000898130.1		c.1447A>G	p.Ile483Val	missense	Exon 11 of 12	ENSP00000568189.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000206 AC: 5 AN: 242302 AF XY: 0.0000153

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000441 AC: 64 AN: 1451520 Hom.: 0 Cov.: 30 AF XY: 0.0000457 AC XY: 33 AN XY: 721318

African (AFR) AF: 0.00 AC: 0 AN: 33018

American (AMR) AF: 0.00 AC: 0 AN: 42522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39328

South Asian (SAS) AF: 0.00 AC: 0 AN: 84094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000560 AC: 62 AN: 1107590

Other (OTH) AF: 0.0000333 AC: 2 AN: 59974

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Developmental and epileptic encephalopathy, 25 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.062
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.86	P
Vest4		0.22
MVP		0.18
MPC		0.24
ClinPred		0.17	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.55
Mutation Taster		=89/11	polymorphism

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: rs143719876; hg19: chr17-6590976;