NM_003057.3:c.215A>G

Variant names:

• chr6-160122150-A-G
• rs745944087
• NM_003057.3:c.215A>G

Variant summary

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

The NM_003057.3(SLC22A1):​c.215A>G​(p.Tyr72Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. 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
	SLC22A1	NM_003057.3	MANE Select	c.215A>G	p.Tyr72Cys	missense	Exon 1 of 11	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.215A>G	p.Tyr72Cys	missense	Exon 1 of 10	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.215A>G	p.Tyr72Cys	missense	Exon 1 of 9	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.215A>G	p.Tyr72Cys	missense	Exon 1 of 11	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.215A>G	p.Tyr72Cys	missense	Exon 1 of 12	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.215A>G	p.Tyr72Cys	missense	Exon 1 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250304 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1460550 Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 726462

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111568

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.095
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.43		Loss of phosphorylation at Y72 (P = 0.0172)
MVP		0.47
MPC		0.66
ClinPred		0.81	D
GERP RS		1.8
PromoterAI		-0.00070	Neutral
Varity_R		0.21
gMVP		0.64
Mutation Taster		=93/7	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: rs745944087; hg19: chr6-160543182; COSMIC: COSV61451554;