chr6-160139813-A-G

Position:

• chr6-160139813-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003057.3(SLC22A1):​c.1222A>G​(p.Met408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,565,314 control chromosomes in the GnomAD database, including 293,961 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.65 (32470 hom., cov: 29)
  • Exomes 𝑓: 0.61 (261491 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.262719E-7).
• BP6: Variant 6-160139813-A-G is Benign according to our data. Variant chr6-160139813-A-G is described in ClinVar as [Benign]. Clinvar id is 1283709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1222A>G	p.Met408Val	missense_variant	7/11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1222A>G	p.Met408Val	missense_variant	7/10		NP_694857.1
SLC22A1	XM_005267103.3	c.1222A>G	p.Met408Val	missense_variant	7/12		XP_005267160.1
SLC22A1	XM_006715552.3	c.1222A>G	p.Met408Val	missense_variant	7/9		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1222A>G	p.Met408Val	missense_variant	7/11	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98648 AN: 151618 Hom.: 32425 Cov.: 29

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.673

GnomAD3 exomes AF: 0.633 AC: 130245 AN: 205896 Hom.: 42197 AF XY: 0.625 AC XY: 70453 AN XY: 112662

Gnomad AFR exome AF: 0.728

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.647

Gnomad EAS exome AF: 0.728

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.545

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.635

GnomAD4 exome AF: 0.605 AC: 855332 AN: 1413578 Hom.: 261491 Cov.: 50 AF XY: 0.606 AC XY: 424000 AN XY: 699724

Gnomad4 AFR exome AF: 0.736

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.651 AC: 98753 AN: 151736 Hom.: 32470 Cov.: 29 AF XY: 0.651 AC XY: 48280 AN XY: 74116

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.676

Alfa AF: 0.608 Hom.: 66152

Bravo AF: 0.672

TwinsUK AF: 0.577 AC: 2141

ALSPAC AF: 0.607 AC: 2338

ESP6500AA AF: 0.726 AC: 3200

ESP6500EA AF: 0.592 AC: 5093

ExAC AF: 0.638 AC: 77502

Asia WGS AF: 0.675 AC: 2344 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 25, 2021

This variant is associated with the following publications: (PMID: 24215657) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0020
DANN	Benign	0.35
DEOGEN2	Benign	0.078	T;T;.;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.21	.;T;T;T
MetaRNN	Benign	8.3e-7	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.7	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.1	N;.;N;N
REVEL	Benign	0.040
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	0.78	T;.;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.018
MPC		0.13
ClinPred		0.030	T
GERP RS		-9.1
Varity_R		0.032
gMVP		0.15

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: rs628031; hg19: chr6-160560845;