chr6-160410858-C-T

Variant names:

• chr6-160410858-C-T
• rs8187720
• NM_021977.4:c.975+12C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.975+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,477,010 control chromosomes in the GnomAD database, including 768 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 0.042 (399 hom., cov: 31)
  • Exomes 𝑓: 0.0072 (369 hom.)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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.975+12C>T		intron	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.975+12C>T		intron	N/A	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6338 AN: 152000 Hom.: 397 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.0382

GnomAD2 exomes AF: 0.0146 AC: 3617 AN: 248352 AF XY: 0.0117

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00717 AC: 9501 AN: 1324892 Hom.: 369 Cov.: 20 AF XY: 0.00662 AC XY: 4413 AN XY: 666456

African (AFR) AF: 0.140 AC: 4358 AN: 31022

American (AMR) AF: 0.0181 AC: 801 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 827 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 38844

South Asian (SAS) AF: 0.000516 AC: 43 AN: 83346

European-Finnish (FIN) AF: 0.0000381 AC: 2 AN: 52540

Middle Eastern (MID) AF: 0.0320 AC: 170 AN: 5312

European-Non Finnish (NFE) AF: 0.00240 AC: 2369 AN: 988562

Other (OTH) AF: 0.0167 AC: 931 AN: 55798

GnomAD4 genome AF: 0.0418 AC: 6351 AN: 152118 Hom.: 399 Cov.: 31 AF XY: 0.0400 AC XY: 2978 AN XY: 74394

African (AFR) AF: 0.135 AC: 5602 AN: 41454

American (AMR) AF: 0.0219 AC: 335 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00312 AC: 212 AN: 68002

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0265 Hom.: 123

Bravo AF: 0.0479

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		0.45
Mutation Taster		=100/0	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: rs8187720; hg19: chr6-160831890;