6-160241560-G-A

Variant summary

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

The NM_003058.4(SLC22A2):c.1415C>T(p.Ser472Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

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

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, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A2	NM_003058.4	c.1415C>T	p.Ser472Leu	missense_variant	9/11	ENST00000366953.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A2	ENST00000366953.8	c.1415C>T	p.Ser472Leu	missense_variant	9/11	1	NM_003058.4	P1
SLC22A2	ENST00000486916.5	n.454C>T		non_coding_transcript_exon_variant	4/6	3
SLC22A2	ENST00000491092.1	n.1312C>T		non_coding_transcript_exon_variant	8/10	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.1415C>T (p.S472L) alteration is located in exon 9 (coding exon 9) of the SLC22A2 gene. This alteration results from a C to T substitution at nucleotide position 1415, causing the serine (S) at amino acid position 472 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.082
Eigen_PC	Benign	0.027
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.24
Sift	Benign	0.046	D
Sift4G	Benign	0.35	T
Polyphen		0.028	B
Vest4		0.63
MutPred		0.69		Loss of catalytic residue at S472 (P = 0.0331);
MVP		0.68
MPC		0.12
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.31
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-160662592;