rs72552763

chr6-160139848-CATG-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PM4_Supporting BA1

The NM_003057.3(SLC22A1):c.1260_1262del(p.Met420del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,526,850 control chromosomes in the GnomAD database, including 24,010 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1808 hom., cov: 28)
  • Exomes 𝑓: 0.17 (22202 hom.)
• Consequence: SLC22A1 NM_003057.3 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_003057.3. Strenght limited to Supporting due to length of the change: 1aa.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.1260_1262del	p.Met420del	inframe_deletion	7/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.1260_1262del	p.Met420del	inframe_deletion	7/10
SLC22A1	XM_005267103.3	c.1260_1262del	p.Met420del	inframe_deletion	7/12
SLC22A1	XM_006715552.3	c.1260_1262del	p.Met420del	inframe_deletion	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1260_1262del	p.Met420del	inframe_deletion	7/11	1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 21145 AN: 139762 Hom.: 1799 Cov.: 28

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.0876

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00274

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.121 AC: 18010 AN: 148824 Hom.: 1455 AF XY: 0.122 AC XY: 9811 AN XY: 80508

Gnomad AFR exome AF: 0.0458

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.0883

Gnomad EAS exome AF: 0.000695

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.172 AC: 239089 AN: 1386984 Hom.: 22202 AF XY: 0.172 AC XY: 117891 AN XY: 684456

Gnomad4 AFR exome AF: 0.0562

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000521

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.151 AC: 21167 AN: 139866 Hom.: 1808 Cov.: 28 AF XY: 0.153 AC XY: 10385 AN XY: 68086

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00274

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.161

Alfa AF: 0.134 Hom.: 320

Bravo AF: 0.141

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72552763; hg19: chr6-160560880;