6-160348247-C-G

Variant names:

• chr6-160348247-C-G
• rs58601841
• NM_021977.4:c.-173C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021977.4(SLC22A3):​c.-173C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 741,014 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (65 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (17 hom.)
• Consequence: SLC22A3 NM_021977.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2165/150934) while in subpopulation AFR AF= 0.049 (2028/41376). AF 95% confidence interval is 0.0472. There are 65 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.-173C>G		upstream_gene_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.-173C>G		upstream_gene_variant		1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2142 AN: 150826 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00594

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.0116

GnomAD4 exome AF: 0.00146 AC: 859 AN: 590080 Hom.: 17 Cov.: 8 AF XY: 0.00134 AC XY: 383 AN XY: 284790

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.00352

Gnomad4 ASJ exome AF: 0.000682

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000243

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.0143 AC: 2165 AN: 150934 Hom.: 65 Cov.: 33 AF XY: 0.0137 AC XY: 1012 AN XY: 73750

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.00594

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000252

Gnomad4 OTH AF: 0.0115

Alfa AF: 0.00197 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs58601841; hg19: chr6-160769279;