rs1399161589

chr17-6690880-C-Achr17-6690880-C-Gchr17-6690880-C-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.1336G>T(p.Ala446Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A446P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

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]

(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=0.12996614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A5	NM_177550.5	c.1336G>T	p.Ala446Ser	missense_variant	10/12	ENST00000433363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A5	ENST00000433363.7	c.1336G>T	p.Ala446Ser	missense_variant	10/12	1	NM_177550.5	P1
	ENST00000634558.1	n.662+853C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	3.5
Dann	Benign	0.80
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;.;L
MutationTaster	Benign	0.86	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.60	N;.;N;.
REVEL	Benign	0.081
Sift	Benign	0.40	T;.;T;.
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.010	B;.;.;.
Vest4		0.35
MutPred		0.60		Gain of glycosylation at A446 (P = 0.029);.;.;Gain of glycosylation at A446 (P = 0.029);
MVP		0.14
MPC		0.27
ClinPred		0.17	T
GERP RS		0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs1399161589; hg19: chr17-6594199; COSMIC: COSV53424808; COSMIC: COSV53424808;