3-38266165-G-T

Variant names:

• chr3-38266165-G-T
• rs113229654
• NM_004256.4:c.305G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004256.4(SLC22A13):​c.305G>T​(p.Arg102Leu) 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. 15/22 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. R102H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A13 NM_004256.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 12 publications found

Genes affected

SLC22A13 (HGNC:8494): (solute carrier family 22 member 13) This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 4. The encoded protein is a transmembrane protein involved in the transport of small molecules. This protein can function to mediate urate uptake and is a high affinity nicotinate exchanger in the kidneys and the intestine. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24766922).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004256.4. 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
	SLC22A13	NM_004256.4	MANE Select	c.305G>T	p.Arg102Leu	missense	Exon 1 of 10	NP_004247.2	Q9Y226-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A13	ENST00000311856.9	TSL:1 MANE Select	c.305G>T	p.Arg102Leu	missense	Exon 1 of 10	ENSP00000310241.3	Q9Y226-1
	SLC22A13	ENST00000415844.1	TSL:2	n.260G>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000395106.1	H0Y4Y1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.9
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.22
Sift	Benign	0.16	T
Sift4G	Benign	0.15	T
Polyphen		0.66	P
Vest4		0.27
MutPred		0.65		Loss of disorder (P = 0.0614)
MVP		0.53
MPC		0.18
ClinPred		0.89	D
GERP RS		1.8
PromoterAI		-0.031	Neutral
Varity_R		0.14
gMVP		0.72
Mutation Taster		=94/6	polymorphism

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: rs113229654; hg19: chr3-38307656;