rs558866003

Variant names:

• chr17-6690882-G-A
• rs558866003
• NM_177550.5:c.1334C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_177550.5(SLC13A5):​c.1334C>T​(p.Pro445Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P445T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.40
• Publications: 0 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40605003).

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.1334C>T	p.Pro445Leu	missense	Exon 10 of 12	NP_808218.1	Q86YT5-1
	SLC13A5	NM_001284509.2		c.1283C>T	p.Pro428Leu	missense	Exon 10 of 12	NP_001271438.1	Q86YT5-3
	SLC13A5	NM_001284510.2		c.1205C>T	p.Pro402Leu	missense	Exon 9 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.1334C>T	p.Pro445Leu	missense	Exon 10 of 12	ENSP00000406220.2	Q86YT5-1
	SLC13A5	ENST00000573648.5	TSL:1	c.1334C>T	p.Pro445Leu	missense	Exon 10 of 11	ENSP00000459372.1	Q86YT5-2
	SLC13A5	ENST00000898130.1		c.1334C>T	p.Pro445Leu	missense	Exon 10 of 12	ENSP00000568189.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251218 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461722 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727164

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111920

Other (OTH) AF: 0.0000662 AC: 4 AN: 60390

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 25 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.4
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.24
Sift	Benign	0.067	T
Sift4G	Uncertain	0.036	D
Polyphen		0.93	P
Vest4		0.51
MutPred		0.61		Gain of stability (P = 0.0227)
MVP		0.33
MPC		0.30
ClinPred		0.47	T
GERP RS		4.1
PromoterAI		-0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.87
Mutation Taster		=70/30	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: rs558866003; hg19: chr17-6594201; COSMIC: COSV53422060; COSMIC: COSV53422060;