rs36103319

Positions:

• chr6-160132375-G-C
• chr6-160132375-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000366963.9(SLC22A1):​c.659G>C​(p.Gly220Ala) 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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G220V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A1 ENST00000366963.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32954797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.659G>C	p.Gly220Ala	missense_variant	3/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.659G>C	p.Gly220Ala	missense_variant	3/10		NP_694857.1
SLC22A1	XM_005267103.3	c.659G>C	p.Gly220Ala	missense_variant	3/12		XP_005267160.1
SLC22A1	XM_006715552.3	c.659G>C	p.Gly220Ala	missense_variant	3/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.659G>C	p.Gly220Ala	missense_variant	3/11	1	NM_003057.3	ENSP00000355930	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.38	T;T;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;D;T;T;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.74	N;N;N;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	N;.;N;N;D
REVEL	Benign	0.23
Sift	Benign	0.34	T;.;T;T;T
Sift4G	Benign	0.59	T;.;T;T;T
Polyphen		0.0080	B;B;P;.;.
Vest4		0.53
MutPred		0.51		Loss of catalytic residue at A219 (P = 0.12);Loss of catalytic residue at A219 (P = 0.12);Loss of catalytic residue at A219 (P = 0.12);Loss of catalytic residue at A219 (P = 0.12);.;
MVP		0.35
MPC		0.35
ClinPred		0.67	D
GERP RS		3.4
Varity_R		0.24
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs36103319; hg19: chr6-160553407;