rs7745775

Variant names:

• chr6-160412436-T-G
• rs7745775
• NM_021977.4:c.975+1590T>G

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+1590T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,072 control chromosomes in the GnomAD database, including 5,144 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 0.26 (5144 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 9 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.975+1590T>G		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+1590T>G		intron_variant	Intron 5 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38774 AN: 151954 Hom.: 5136 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.255 AC: 38804 AN: 152072 Hom.: 5144 Cov.: 32 AF XY: 0.259 AC XY: 19231 AN XY: 74346

African (AFR) AF: 0.311 AC: 12898 AN: 41464

American (AMR) AF: 0.328 AC: 5004 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1227 AN: 5178

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2826 AN: 10570

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13928 AN: 67994

Other (OTH) AF: 0.272 AC: 575 AN: 2112

Alfa AF: 0.222 Hom.: 5541

Bravo AF: 0.262

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		0.27
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: rs7745775; hg19: chr6-160833468;