6-160132375-G-T

Variant summary

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

The NM_003057.3(SLC22A1):c.659G>T(p.Gly220Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,606,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: SLC22A1 NM_003057.3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19405201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.659G>T	p.Gly220Val	missense_variant	3/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.659G>T	p.Gly220Val	missense_variant	3/10
SLC22A1	XM_005267103.3	c.659G>T	p.Gly220Val	missense_variant	3/12
SLC22A1	XM_006715552.3	c.659G>T	p.Gly220Val	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.659G>T	p.Gly220Val	missense_variant	3/11	1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000185 AC: 45 AN: 243196 Hom.: 0 AF XY: 0.000175 AC XY: 23 AN XY: 131118

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000903

Gnomad OTH exome AF: 0.000342

GnomAD4 exome AF: 0.000101 AC: 147 AN: 1453874 Hom.: 0 Cov.: 31 AF XY: 0.0000830 AC XY: 60 AN XY: 722756

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.000685

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: 0.0000623

Gnomad4 OTH exome AF: 0.000216

GnomAD4 genome AF: 0.000492 AC: 75 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74496

Gnomad4 AFR AF: 0.00132

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000118 Hom.: 0

Bravo AF: 0.000612

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000222 AC: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Uncertain	0.080
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.8	L;L;L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.5	D;.;D;D;D
REVEL	Uncertain	0.45
Sift	Benign	0.050	D;.;T;D;T
Sift4G	Benign	0.077	T;.;T;T;D
Polyphen		0.57	P;P;D;.;.
Vest4		0.73
MVP		0.48
MPC		0.66
ClinPred		0.12	T
GERP RS		3.4
Varity_R		0.56
gMVP		0.63

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;