6-3359103-T-C

Variant names:

• chr6-3359103-T-C
• rs4959235
• NM_015482.2:c.914-35101A>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.914-35101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,262 control chromosomes in the GnomAD database, including 68,575 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 0.95 (68575 hom., cov: 31)
• Consequence: SLC22A23 NM_015482.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 25 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 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.914-35101A>G		intron	N/A	NP_056297.1
	SLC22A23	NM_001382317.1		c.914-35101A>G		intron	N/A	NP_001369246.1
	SLC22A23	NM_001286455.1		c.71-35101A>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.914-35101A>G		intron	N/A	ENSP00000385028.3
	SLC22A23	ENST00000485307.5	TSL:1	c.398-35101A>G		intron	N/A	ENSP00000418134.1
	SLC22A23	ENST00000380302.8	TSL:1	c.71-35101A>G		intron	N/A	ENSP00000369657.4

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144219 AN: 152144 Hom.: 68523 Cov.: 31

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.948 AC: 144331 AN: 152262 Hom.: 68575 Cov.: 31 AF XY: 0.945 AC XY: 70330 AN XY: 74436

African (AFR) AF: 0.987 AC: 41020 AN: 41546

American (AMR) AF: 0.873 AC: 13346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3390 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5178

South Asian (SAS) AF: 0.984 AC: 4738 AN: 4816

European-Finnish (FIN) AF: 0.895 AC: 9501 AN: 10612

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64008 AN: 68026

Other (OTH) AF: 0.954 AC: 2017 AN: 2114

Alfa AF: 0.945 Hom.: 241090

Bravo AF: 0.948

Asia WGS AF: 0.989 AC: 3439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.29
PhyloP100		-1.1
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: rs4959235; hg19: chr6-3359337;