rs8187725

Variant names:

• chr6-160437122-C-A
• rs8187725
• NM_021977.4:c.1199C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160437122-C-A
• chr6-160437122-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021977.4(SLC22A3):​c.1199C>A​(p.Thr400Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC22A3 NM_021977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• Publications: 19 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.1199C>A	p.Thr400Asn	missense_variant	Exon 7 of 11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1199C>A	p.Thr400Asn	missense_variant	Exon 7 of 11	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251262 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

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: 0.00000274 AC: 4 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.57		Gain of methylation at R403 (P = 0.2224);
MVP		0.89
MPC		1.2
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.74
gMVP		0.80
Mutation Taster		=55/45	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: rs8187725; hg19: chr6-160858154;