17-28491736-C-G

Variant names:

• chr17-28491736-C-G
• NM_003984.4:c.762C>G
• SLC13A2 p.Phe254Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003984.4(SLC13A2):​c.762C>G​(p.Phe254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 0 publications found

Genes affected

SLC13A2 (HGNC:10917): (solute carrier family 13 member 2) The protein encoded by this gene is a sodium-coupled citrate transporter that is regulated by the chaperone activity of cyclophilin b. The encoded protein may play a role in the formation of kidney stones. [provided by RefSeq, Oct 2016]

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003984.4. 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
	SLC13A2	NM_003984.4	MANE Select	c.762C>G	p.Phe254Leu	missense	Exon 6 of 12	NP_003975.1	Q13183-1
	SLC13A2	NM_001145975.2		c.909C>G	p.Phe303Leu	missense	Exon 6 of 12	NP_001139447.1	Q13183-3
	SLC13A2	NM_001346683.2		c.630C>G	p.Phe210Leu	missense	Exon 7 of 13	NP_001333612.1	J3QL78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.762C>G	p.Phe254Leu	missense	Exon 6 of 12	ENSP00000316202.6	Q13183-1
	RSKR	ENST00000481916.6	TSL:1	n.*1196-35627G>C		intron	N/A	ENSP00000436369.2	Q96LW2-2
	SLC13A2	ENST00000855217.1		c.909C>G	p.Phe303Leu	missense	Exon 6 of 12	ENSP00000525276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.56
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Varity_R		0.79
gMVP		0.88

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-26818754;