rs72552763

Variant names:

• chr6-160139848-CATG-C
• rs72552763
• NM_003057.3:c.1260_1262delGAT

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PM4_Supporting BA1

The NM_003057.3(SLC22A1):​c.1260_1262delGAT​(p.Met420del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 100 publications found

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]

ENSG00000301636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1260_1262delGAT	p.Met420del	disruptive_inframe_deletion	Exon 7 of 11	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1260_1262delGAT	p.Met420del	disruptive_inframe_deletion	Exon 7 of 10		NP_694857.1
SLC22A1	NM_001437335.1	c.1260_1262delGAT	p.Met420del	disruptive_inframe_deletion	Exon 7 of 9		NP_001424264.1
SLC22A1	XM_005267103.3	c.1260_1262delGAT	p.Met420del	disruptive_inframe_deletion	Exon 7 of 12		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1260_1262delGAT	p.Met420del	disruptive_inframe_deletion	Exon 7 of 11	1	NM_003057.3	ENSP00000355930.4

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

GnomAD2 exomes AF: 0.121 AC: 18010 AN: 148824 AF XY: 0.122

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 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

African (AFR) AF: 0.0562 AC: 1707 AN: 30376

American (AMR) AF: 0.262 AC: 8102 AN: 30920

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2767 AN: 21782

East Asian (EAS) AF: 0.000521 AC: 20 AN: 38374

South Asian (SAS) AF: 0.171 AC: 12753 AN: 74436

European-Finnish (FIN) AF: 0.144 AC: 7364 AN: 51122

Middle Eastern (MID) AF: 0.132 AC: 716 AN: 5404

European-Non Finnish (NFE) AF: 0.183 AC: 196654 AN: 1077538

Other (OTH) AF: 0.158 AC: 9006 AN: 57032

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

African (AFR) AF: 0.0691 AC: 2428 AN: 35138

American (AMR) AF: 0.244 AC: 3403 AN: 13938

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 418 AN: 3292

East Asian (EAS) AF: 0.00274 AC: 12 AN: 4372

South Asian (SAS) AF: 0.178 AC: 774 AN: 4358

European-Finnish (FIN) AF: 0.166 AC: 1650 AN: 9960

Middle Eastern (MID) AF: 0.165 AC: 44 AN: 266

European-Non Finnish (NFE) AF: 0.183 AC: 12061 AN: 65806

Other (OTH) AF: 0.161 AC: 302 AN: 1880

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=80/20	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72552763; hg19: chr6-160560880; COSMIC: COSV61451420;