6-3328249-T-C

Variant names:

• chr6-3328249-T-C
• rs4128535
• NM_015482.2:c.914-4247A>G

Variant summary

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

The NM_015482.2(SLC22A23):​c.914-4247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,550 control chromosomes in the GnomAD database, including 6,078 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 (6078 hom., cov: 31)
• Consequence: SLC22A23 NM_015482.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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.914-4247A>G		intron	N/A	NP_056297.1
	SLC22A23	NM_001382317.1		c.914-4247A>G		intron	N/A	NP_001369246.1
	SLC22A23	NM_001286455.1		c.71-4247A>G		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.914-4247A>G		intron	N/A	ENSP00000385028.3
	SLC22A23	ENST00000485307.5	TSL:1	c.398-4247A>G		intron	N/A	ENSP00000418134.1
	SLC22A23	ENST00000380302.8	TSL:1	c.71-4247A>G		intron	N/A	ENSP00000369657.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38232 AN: 151432 Hom.: 6054 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.253 AC: 38304 AN: 151550 Hom.: 6078 Cov.: 31 AF XY: 0.249 AC XY: 18414 AN XY: 74032

African (AFR) AF: 0.447 AC: 18427 AN: 41210

American (AMR) AF: 0.174 AC: 2634 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 781 AN: 3462

East Asian (EAS) AF: 0.233 AC: 1205 AN: 5174

South Asian (SAS) AF: 0.272 AC: 1293 AN: 4754

European-Finnish (FIN) AF: 0.0978 AC: 1030 AN: 10532

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12074 AN: 67936

Other (OTH) AF: 0.247 AC: 519 AN: 2104

Alfa AF: 0.213 Hom.: 522

Bravo AF: 0.267

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.4
DANN	Benign	0.35
PhyloP100		-0.13
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: rs4128535; hg19: chr6-3328483;