11-63143607-G-C

Variant names:

• chr11-63143607-G-C
• rs1939748
• NM_001136506.2:c.173C>G

Variant summary

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

The NM_001136506.2(SLC22A24):​c.173C>G​(p.Thr58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,574,552 control chromosomes in the GnomAD database, including 551,601 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (45537 hom., cov: 31)
  • Exomes 𝑓: 0.84 (506064 hom.)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 28 publications found

Genes affected

SLC22A24 (HGNC:28542): (solute carrier family 22 member 24) SLC22A24 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 (MetaRNN=9.0526675E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136506.2. 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
	SLC22A24	NM_001136506.2	MANE Select	c.173C>G	p.Thr58Ser	missense	Exon 1 of 10	NP_001129978.2
	SLC22A24	NM_173586.3		c.173C>G	p.Thr58Ser	missense	Exon 1 of 4	NP_775857.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A24	ENST00000612278.4	TSL:5 MANE Select	c.173C>G	p.Thr58Ser	missense	Exon 1 of 10	ENSP00000480336.1
	SLC22A24	ENST00000417740.5	TSL:5	c.173C>G	p.Thr58Ser	missense	Exon 1 of 10	ENSP00000396586.1
	SLC22A24	ENST00000326192.5	TSL:1	c.173C>G	p.Thr58Ser	missense	Exon 1 of 4	ENSP00000321549.5

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115589 AN: 151964 Hom.: 45532 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.796

GnomAD2 exomes AF: 0.836 AC: 180972 AN: 216350 AF XY: 0.840

Gnomad AFR exome AF: 0.533

Gnomad AMR exome AF: 0.894

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.917

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.847

Gnomad OTH exome AF: 0.835

GnomAD4 exome AF: 0.842 AC: 1197282 AN: 1422470 Hom.: 506064 Cov.: 51 AF XY: 0.842 AC XY: 594048 AN XY: 705606

African (AFR) AF: 0.531 AC: 16905 AN: 31834

American (AMR) AF: 0.887 AC: 35484 AN: 39994

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 18368 AN: 23928

East Asian (EAS) AF: 0.907 AC: 33957 AN: 37428

South Asian (SAS) AF: 0.832 AC: 65868 AN: 79188

European-Finnish (FIN) AF: 0.885 AC: 46066 AN: 52074

Middle Eastern (MID) AF: 0.783 AC: 4380 AN: 5592

European-Non Finnish (NFE) AF: 0.848 AC: 927866 AN: 1093672

Other (OTH) AF: 0.823 AC: 48388 AN: 58760

GnomAD4 genome AF: 0.760 AC: 115622 AN: 152082 Hom.: 45537 Cov.: 31 AF XY: 0.763 AC XY: 56729 AN XY: 74324

African (AFR) AF: 0.536 AC: 22213 AN: 41442

American (AMR) AF: 0.831 AC: 12702 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2684 AN: 3470

East Asian (EAS) AF: 0.902 AC: 4670 AN: 5180

South Asian (SAS) AF: 0.844 AC: 4064 AN: 4818

European-Finnish (FIN) AF: 0.882 AC: 9327 AN: 10574

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57344 AN: 67992

Other (OTH) AF: 0.789 AC: 1667 AN: 2112

Alfa AF: 0.825 Hom.: 31661

Bravo AF: 0.750

TwinsUK AF: 0.845 AC: 3133

ALSPAC AF: 0.851 AC: 3279

ESP6500AA AF: 0.518 AC: 717

ESP6500EA AF: 0.828 AC: 2635

ExAC AF: 0.826 AC: 100132

Asia WGS AF: 0.825 AC: 2866 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	0.0041
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	9.1e-7	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.11
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.086
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.015
MutPred		0.40		Gain of disorder (P = 0.0571)
MPC		0.0090
ClinPred		0.051	T
GERP RS		2.3
gMVP		0.11
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: rs1939748; hg19: chr11-62911079; COSMIC: COSV58223667;