6-160430734-T-C

Variant names:

• chr6-160430734-T-C
• rs376563
• NM_021977.4:c.976-6046T>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.976-6046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,114 control chromosomes in the GnomAD database, including 27,538 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 0.59 (27538 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 23 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.976-6046T>C		intron_variant	Intron 5 of 10	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.976-6046T>C		intron_variant	Intron 5 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90298 AN: 151996 Hom.: 27495 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.594 AC: 90401 AN: 152114 Hom.: 27538 Cov.: 33 AF XY: 0.591 AC XY: 43972 AN XY: 74352

African (AFR) AF: 0.735 AC: 30498 AN: 41476

American (AMR) AF: 0.606 AC: 9266 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3296 AN: 5166

South Asian (SAS) AF: 0.502 AC: 2415 AN: 4810

European-Finnish (FIN) AF: 0.524 AC: 5544 AN: 10588

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35704 AN: 67992

Other (OTH) AF: 0.583 AC: 1233 AN: 2114

Alfa AF: 0.547 Hom.: 62737

Bravo AF: 0.605

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.53
PhyloP100		0.15
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: rs376563; hg19: chr6-160851766; COSMIC: COSV51711777;