6-3294590-G-T

Variant names:

• chr6-3294590-G-T
• rs9378357
• NM_015482.2:c.1210+3501C>A

Variant summary

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

The NM_015482.2(SLC22A23):​c.1210+3501C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,152 control chromosomes in the GnomAD database, including 4,773 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 0.20 (4773 hom., cov: 33)
• Consequence: SLC22A23 NM_015482.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 7 publications found

Genes affected

SLC22A23 (HGNC:21106): (solute carrier family 22 member 23) SLC22A23 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).[supplied by OMIM, Mar 2008]

PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015482.2. 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
	SLC22A23	NM_015482.2	MANE Select	c.1210+3501C>A		intron	N/A	NP_056297.1
	SLC22A23	NM_001382317.1		c.1210+3501C>A		intron	N/A	NP_001369246.1
	SLC22A23	NM_001286455.1		c.367+3501C>A		intron	N/A	NP_001273384.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A23	ENST00000406686.8	TSL:5 MANE Select	c.1210+3501C>A		intron	N/A	ENSP00000385028.3
	SLC22A23	ENST00000485307.5	TSL:1	c.694+3501C>A		intron	N/A	ENSP00000418134.1
	SLC22A23	ENST00000380302.8	TSL:1	c.367+3501C>A		intron	N/A	ENSP00000369657.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29669 AN: 152032 Hom.: 4758 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.195 AC: 29719 AN: 152152 Hom.: 4773 Cov.: 33 AF XY: 0.195 AC XY: 14489 AN XY: 74386

African (AFR) AF: 0.429 AC: 17777 AN: 41464

American (AMR) AF: 0.148 AC: 2270 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1703 AN: 5162

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4818

European-Finnish (FIN) AF: 0.0474 AC: 503 AN: 10606

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.0744 AC: 5058 AN: 68012

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.125 Hom.: 5346

Bravo AF: 0.212

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-1.9
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: rs9378357; hg19: chr6-3294824;