17-28489328-G-T

Variant names:

• chr17-28489328-G-T
• rs202116509
• NM_003984.4:c.217G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346684.2(SLC13A2):​c.-59G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC13A2 NM_001346684.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041558713).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346684.2. 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.217G>T	p.Val73Leu	missense	Exon 2 of 12	NP_003975.1	Q13183-1
	SLC13A2	NM_001346684.2		c.-59G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001333613.1
	SLC13A2	NM_001145975.2		c.217G>T	p.Val73Leu	missense	Exon 2 of 12	NP_001139447.1	Q13183-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.217G>T	p.Val73Leu	missense	Exon 2 of 12	ENSP00000316202.6	Q13183-1
	RSKR	ENST00000481916.6	TSL:1	n.*1196-33219C>A		intron	N/A	ENSP00000436369.2	Q96LW2-2
	SLC13A2	ENST00000855217.1		c.217G>T	p.Val73Leu	missense	Exon 2 of 12	ENSP00000525276.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.62
DANN	Benign	0.74
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.4	N
PhyloP100		3.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.53		Loss of catalytic residue at V73 (P = 0.0397)
MVP		0.048
MPC		0.27
ClinPred		0.049	T
GERP RS		0.97
Varity_R		0.054
gMVP		0.40

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

Other links and lift over

dbSNP: rs202116509; hg19: chr17-26816346;