rs2504916

chr6-160402996-T-Achr6-160402996-T-Cchr6-160402996-T-G

Variant summary

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

The NM_021977.4(SLC22A3):c.534-4045T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 151,250 control chromosomes in the GnomAD database, including 48,508 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 0.80 (48508 hom., cov: 29)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.534-4045T>A		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.534-4045T>A		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 120767 AN: 151132 Hom.: 48459 Cov.: 29

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.799 AC: 120876 AN: 151250 Hom.: 48508 Cov.: 29 AF XY: 0.802 AC XY: 59263 AN XY: 73936

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.813

Alfa AF: 0.784 Hom.: 26010

Bravo AF: 0.797

Asia WGS AF: 0.945 AC: 3271 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.3
Dann	Benign	0.52

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: rs2504916; hg19: chr6-160824028; COSMIC: COSV51711590;