rs1867351

chr6-160122091-T-Achr6-160122091-T-C

Variant summary

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

The NM_003057.3(SLC22A1):c.156T>A(p.Ser52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,598 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.156T>A	p.Ser52Arg	missense_variant	1/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.156T>A	p.Ser52Arg	missense_variant	1/10
SLC22A1	XM_005267103.3	c.156T>A	p.Ser52Arg	missense_variant	1/12
SLC22A1	XM_006715552.3	c.156T>A	p.Ser52Arg	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.156T>A	p.Ser52Arg	missense_variant	1/11	1	NM_003057.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;.;.
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.1	M;M;M;M
MutationTaster	Benign	0.19	P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;.;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.090	T;.;T;T
Sift4G	Benign	0.35	T;.;T;T
Polyphen		0.91	P;P;P;.
Vest4		0.47
MutPred		0.55		Loss of glycosylation at S52 (P = 0.0326);Loss of glycosylation at S52 (P = 0.0326);Loss of glycosylation at S52 (P = 0.0326);Loss of glycosylation at S52 (P = 0.0326);
MVP		0.49
MPC		0.42
ClinPred		0.90	D
GERP RS		2.6
Varity_R		0.16
gMVP		0.73

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: rs1867351; hg19: chr6-160543123;