rs1939748

Positions:

• chr11-63143607-G-C
• chr11-63143607-G-T

Variant summary

Our verdict is Benign. Variant got -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. 11/17 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A24	NM_001136506.2	c.173C>G	p.Thr58Ser	missense_variant	1/10	ENST00000612278.4
SLC22A24	NM_173586.3	c.173C>G	p.Thr58Ser	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A24	ENST00000612278.4	c.173C>G	p.Thr58Ser	missense_variant	1/10	5	NM_001136506.2	P4
SLC22A24	ENST00000326192.5	c.173C>G	p.Thr58Ser	missense_variant	1/4	1
SLC22A24	ENST00000417740.5	c.173C>G	p.Thr58Ser	missense_variant	1/10	5		A1

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

GnomAD3 exomes AF: 0.836 AC: 180972 AN: 216350 Hom.: 76583 AF XY: 0.840 AC XY: 98060 AN XY: 116760

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 SAS exome AF: 0.829

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

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.907

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.823

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

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.789

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 v4.3

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;T;.
MetaRNN	Benign	9.1e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.8	D;.;D
REVEL	Benign	0.086
Sift	Benign	0.12	T;.;T
Sift4G	Benign	0.19	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.015
MutPred		0.40		Gain of disorder (P = 0.0571);Gain of disorder (P = 0.0571);Gain of disorder (P = 0.0571);
MPC		0.0090
ClinPred		0.051	T
GERP RS		2.3
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs1939748; hg19: chr11-62911079; COSMIC: COSV58223667;