6-160355293-A-G

Position:

• chr6-160355293-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.429+6445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,810 control chromosomes in the GnomAD database, including 20,760 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 0.52 (20760 hom., cov: 30)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.429+6445A>G		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.429+6445A>G		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78554 AN: 151692 Hom.: 20724 Cov.: 30

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.518 AC: 78644 AN: 151810 Hom.: 20760 Cov.: 30 AF XY: 0.515 AC XY: 38194 AN XY: 74190

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.509

Alfa AF: 0.498 Hom.: 21561

Bravo AF: 0.524

Asia WGS AF: 0.393 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs675162; hg19: chr6-160776325;