6-160368509-G-C

Position:

• chr6-160368509-G-C

Variant summary

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

The NM_021977.4(SLC22A3):​c.429+19661G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,960 control chromosomes in the GnomAD database, including 6,367 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 0.28 (6367 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.429+19661G>C		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.429+19661G>C		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42366 AN: 151842 Hom.: 6354 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.279 AC: 42412 AN: 151960 Hom.: 6367 Cov.: 32 AF XY: 0.283 AC XY: 20992 AN XY: 74240

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.307

Alfa AF: 0.286 Hom.: 884

Bravo AF: 0.283

Asia WGS AF: 0.379 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.56

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: rs443043; hg19: chr6-160789541;