NM_177550.5:c.1646G>C

Variant names:

• chr17-6686268-C-G
• NM_177550.5:c.1646G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_177550.5(SLC13A5):​c.1646G>C​(p.Arg549Pro) variant causes a missense change involving the alteration of a non-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. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: SLC13A5 NM_177550.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC13A5	NM_177550.5	c.1646G>C	p.Arg549Pro	missense_variant	Exon 12 of 12	ENST00000433363.7	NP_808218.1
SLC13A5	NM_001284509.2	c.1595G>C	p.Arg532Pro	missense_variant	Exon 12 of 12		NP_001271438.1
SLC13A5	NM_001284510.2	c.1517G>C	p.Arg506Pro	missense_variant	Exon 11 of 11		NP_001271439.1
SLC13A5	NM_001143838.3	c.1508G>C	p.Arg503Pro	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.1646G>C	p.Arg549Pro	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: 0.00000138 AC XY: 1 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.;.;.
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.73	T;T;T;D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.73	N;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	.;.;D;.
REVEL	Benign	0.21
Sift	Benign	0.20	.;.;T;.
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.90	P;.;.;.
Vest4		0.58
MutPred		0.74		Loss of methylation at R549 (P = 0.0223);.;.;.;
MVP		0.30
MPC		1.0
ClinPred		0.92	D
GERP RS		1.9
Varity_R		0.74
gMVP		0.90

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: chr17-6589587;