rs202208840

Variant names:

• chr17-6686286-G-A
• NM_177550.5:c.1628C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6686286-G-A
• chr17-6686286-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_177550.5(SLC13A5):​c.1628C>T​(p.Ala543Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A543D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5	c.1628C>T	p.Ala543Val	missense_variant	Exon 12 of 12	ENST00000433363.7	NP_808218.1
SLC13A5	NM_001284509.2	c.1577C>T	p.Ala526Val	missense_variant	Exon 12 of 12		NP_001271438.1
SLC13A5	NM_001284510.2	c.1499C>T	p.Ala500Val	missense_variant	Exon 11 of 11		NP_001271439.1
SLC13A5	NM_001143838.3	c.1490C>T	p.Ala497Val	missense_variant	Exon 11 of 11		NP_001137310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A5	ENST00000433363.7	c.1628C>T	p.Ala543Val	missense_variant	Exon 12 of 12	1	NM_177550.5	ENSP00000406220.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	.;.;D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0040	.;.;D;.
Sift4G	Uncertain	0.050	T;D;T;D
Polyphen		0.0030	B;.;.;.
Vest4		0.40
MutPred		0.79		Loss of catalytic residue at A543 (P = 0.1984);.;.;.;
MVP		0.32
MPC		0.31
ClinPred		0.97	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-6589605;