6-160442500-T-C

Variant names:

• chr6-160442500-T-C
• rs2048327
• NM_021977.4:c.1289-261T>C

Variant summary

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

The NM_021977.4(SLC22A3):​c.1289-261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,184 control chromosomes in the GnomAD database, including 7,753 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 0.29 (7753 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 126 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.1289-261T>C		intron	N/A	NP_068812.1	O75751

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.1289-261T>C		intron	N/A	ENSP00000275300.2	O75751
	SLC22A3	ENST00000855214.1		c.1379-261T>C		intron	N/A	ENSP00000525273.1
	SLC22A3	ENST00000855213.1		c.743-261T>C		intron	N/A	ENSP00000525272.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43672 AN: 152066 Hom.: 7740 Cov.: 33

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43698 AN: 152184 Hom.: 7753 Cov.: 33 AF XY: 0.285 AC XY: 21208 AN XY: 74416

African (AFR) AF: 0.0837 AC: 3479 AN: 41542

American (AMR) AF: 0.431 AC: 6591 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2406 AN: 5176

South Asian (SAS) AF: 0.275 AC: 1329 AN: 4828

European-Finnish (FIN) AF: 0.296 AC: 3136 AN: 10590

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.367 AC: 24945 AN: 67978

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.343 Hom.: 42876

Bravo AF: 0.290

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.38
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: rs2048327; hg19: chr6-160863532; COSMIC: COSV51711838;