6-160249250-A-G

Variant names:

• chr6-160249250-A-G
• rs316019
• NM_003058.4:c.808T>C

Variant summary

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

The NM_003058.4(SLC22A2):​c.808T>C​(p.Ser270Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.808T>C	p.Ser270Pro	missense_variant	Exon 4 of 11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8	c.808T>C	p.Ser270Pro	missense_variant	Exon 4 of 11	1	NM_003058.4	ENSP00000355920.3
SLC22A2	ENST00000366952.1	c.745T>C	p.Ser249Pro	missense_variant	Exon 6 of 8	5		ENSP00000355919.1
SLC22A2	ENST00000491092.1	n.705T>C		non_coding_transcript_exon_variant	Exon 3 of 10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.64	D;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.9	H;.
PhyloP100		2.5
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.016	D;D
Vest4		0.41
ClinPred		0.61	D
GERP RS		-2.3
Varity_R		0.80
gMVP		0.93
Mutation Taster		=85/15	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: rs316019; hg19: chr6-160670282;