chr17-6686332-T-A

Variant names:

• chr17-6686332-T-A
• NM_177550.5:c.1582A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_177550.5(SLC13A5):​c.1582A>T​(p.Thr528Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20337185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5	c.1582A>T	p.Thr528Ser	missense_variant	Exon 12 of 12	ENST00000433363.7	NP_808218.1
SLC13A5	NM_001284509.2	c.1531A>T	p.Thr511Ser	missense_variant	Exon 12 of 12		NP_001271438.1
SLC13A5	NM_001284510.2	c.1453A>T	p.Thr485Ser	missense_variant	Exon 11 of 11		NP_001271439.1
SLC13A5	NM_001143838.3	c.1444A>T	p.Thr482Ser	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.1582A>T	p.Thr528Ser	missense_variant	Exon 12 of 12	1	NM_177550.5	ENSP00000406220.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727216

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: 8.99e-7

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	Benign	0.16
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	.;.;N;.
REVEL	Benign	0.057
Sift	Benign	0.13	.;.;T;.
Sift4G	Benign	0.093	T;T;T;T
Polyphen		0.16	B;.;.;.
Vest4		0.050
MutPred		0.69		Gain of glycosylation at T528 (P = 0.0758);.;.;.;
MVP		0.28
MPC		0.26
ClinPred		0.26	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr17-6589651;