NM_021977.4:c.-108_-107delGA

Variant names:

• chr6-160348311-CGA-C
• rs60515630
• NM_021977.4:c.-108_-107delGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021977.4(SLC22A3):​c.-108_-107delGA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,242,332 control chromosomes in the GnomAD database, including 331 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (203 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (128 hom.)
• Consequence: SLC22A3 NM_021977.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 4 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.-108_-107delGA		upstream_gene	N/A	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.-108_-107delGA		upstream_gene	N/A	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4559 AN: 151016 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0278

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000971

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.0319

GnomAD4 exome AF: 0.00469 AC: 5123 AN: 1091210 Hom.: 128 AF XY: 0.00452 AC XY: 2372 AN XY: 525240

African (AFR) AF: 0.0935 AC: 2018 AN: 21574

American (AMR) AF: 0.0181 AC: 145 AN: 8026

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 479 AN: 14732

East Asian (EAS) AF: 0.00 AC: 0 AN: 24958

South Asian (SAS) AF: 0.000527 AC: 20 AN: 37968

European-Finnish (FIN) AF: 0.0000761 AC: 2 AN: 26270

Middle Eastern (MID) AF: 0.0292 AC: 88 AN: 3014

European-Non Finnish (NFE) AF: 0.00201 AC: 1831 AN: 910130

Other (OTH) AF: 0.0121 AC: 540 AN: 44538

GnomAD4 genome AF: 0.0302 AC: 4568 AN: 151122 Hom.: 203 Cov.: 33 AF XY: 0.0291 AC XY: 2147 AN XY: 73838

African (AFR) AF: 0.0943 AC: 3904 AN: 41378

American (AMR) AF: 0.0182 AC: 276 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 96 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.0000971 AC: 1 AN: 10296

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.00315 AC: 213 AN: 67586

Other (OTH) AF: 0.0306 AC: 64 AN: 2094

Alfa AF: 0.0189 Hom.: 18

Bravo AF: 0.0353

Asia WGS AF: 0.00558 AC: 19 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60515630; hg19: chr6-160769343;