chr6-160387116-C-T

Variant names:

• chr6-160387116-C-T
• rs420038
• NM_021977.4:c.430-10863C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021977.4(SLC22A3):​c.430-10863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,148 control chromosomes in the GnomAD database, including 5,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5086 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149
• Publications: 14 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]

LOC124901453 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-160387116-C-T is Benign according to our data. Variant chr6-160387116-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.430-10863C>T		intron	N/A	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.430-10863C>T		intron	N/A	ENSP00000275300.2
	ENSG00000287656	ENST00000663900.1		n.-182G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37950 AN: 152030 Hom.: 5083 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.250 AC: 37969 AN: 152148 Hom.: 5086 Cov.: 33 AF XY: 0.253 AC XY: 18785 AN XY: 74382

African (AFR) AF: 0.165 AC: 6846 AN: 41538

American (AMR) AF: 0.196 AC: 3000 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3468

East Asian (EAS) AF: 0.370 AC: 1904 AN: 5150

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3095 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19287 AN: 67982

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.275 Hom.: 2842

Bravo AF: 0.239

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30561001)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.60
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: rs420038; hg19: chr6-160808148;