6-160419220-G-T

Variant names:

• chr6-160419220-G-T
• rs7758229
• NM_021977.4:c.975+8374G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.975+8374G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,024 control chromosomes in the GnomAD database, including 5,423 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 0.25 (5423 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788
• Publications: 94 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.975+8374G>T		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.975+8374G>T		intron_variant	Intron 5 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37315 AN: 151906 Hom.: 5426 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.245 AC: 37319 AN: 152024 Hom.: 5423 Cov.: 32 AF XY: 0.241 AC XY: 17939 AN XY: 74302

African (AFR) AF: 0.0992 AC: 4112 AN: 41470

American (AMR) AF: 0.242 AC: 3690 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1278 AN: 5176

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4822

European-Finnish (FIN) AF: 0.274 AC: 2888 AN: 10532

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22351 AN: 67966

Other (OTH) AF: 0.236 AC: 498 AN: 2114

Alfa AF: 0.297 Hom.: 32254

Bravo AF: 0.233

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.44
PhyloP100		-0.79
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: rs7758229; hg19: chr6-160840252; COSMIC: COSV51710325;