rs8177507

Positions:

• chr6-160256637-C-G
• chr6-160256637-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003058.4(SLC22A2):​c.495G>C​(p.Met165Ile) 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. 16/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17331153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.495G>C	p.Met165Ile	missense_variant	2/11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8	c.495G>C	p.Met165Ile	missense_variant	2/11	1	NM_003058.4	ENSP00000355920	P1
SLC22A2	ENST00000366952.1	c.432G>C	p.Met144Ile	missense_variant	4/8	5		ENSP00000355919
SLC22A2	ENST00000491092.1	n.415+1707G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.6
DANN	Benign	0.53
DEOGEN2	Benign	0.089	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.10	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.12	N;N
REVEL	Benign	0.13
Sift	Benign	0.38	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.55		Gain of catalytic residue at M165 (P = 0.0184);.;
MVP		0.31
MPC		0.076
ClinPred		0.054	T
GERP RS		4.9
Varity_R		0.19
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

LitVar

Other links and lift over

dbSNP: rs8177507; hg19: chr6-160677669;