6-160430734-T-C

Position:

• chr6-160430734-T-C

Variant summary

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

The ENST00000275300.3(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 ENST00000275300.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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=-0.9).
• 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/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.976-6046T>C		intron_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.976-6046T>C		intron_variant		1	NM_021977.4	ENSP00000275300	P1

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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.583

Alfa AF: 0.531 Hom.: 36065

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

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: rs376563; hg19: chr6-160851766; COSMIC: COSV51711777;