11-63096046-A-G

Variant names:

• chr11-63096046-A-G
• rs7113279
• NM_001136506.2:c.1015T>C

Variant summary

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

The NM_001136506.2(SLC22A24):​c.1015T>C​(p.Ser339Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,549,930 control chromosomes in the GnomAD database, including 217,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 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 0.50 (19133 hom., cov: 33)
  • Exomes 𝑓: 0.53 (197902 hom.)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 21 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=0.0041344464).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A24	NM_001136506.2	MANE Select	c.1015T>C	p.Ser339Pro	missense	Exon 6 of 10	NP_001129978.2	Q8N4F4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A24	ENST00000612278.4	TSL:5 MANE Select	c.1015T>C	p.Ser339Pro	missense	Exon 6 of 10	ENSP00000480336.1	Q8N4F4-2
	SLC22A24	ENST00000417740.5	TSL:5	c.1015T>C	p.Ser339Pro	missense	Exon 6 of 10	ENSP00000396586.1	Q8N4F4-3
	SLC22A24	ENST00000908490.1		c.463T>C	p.Ser155Pro	missense	Exon 2 of 3	ENSP00000578549.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75935 AN: 151840 Hom.: 19134 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.512 AC: 78625 AN: 153562 AF XY: 0.516

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.544

Gnomad FIN exome AF: 0.481

Gnomad NFE exome AF: 0.533

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.531 AC: 742346 AN: 1397972 Hom.: 197902 Cov.: 41 AF XY: 0.531 AC XY: 366050 AN XY: 689496

African (AFR) AF: 0.448 AC: 14123 AN: 31536

American (AMR) AF: 0.499 AC: 17793 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 13563 AN: 25110

East Asian (EAS) AF: 0.580 AC: 20699 AN: 35704

South Asian (SAS) AF: 0.503 AC: 39819 AN: 79138

European-Finnish (FIN) AF: 0.479 AC: 23592 AN: 49258

Middle Eastern (MID) AF: 0.528 AC: 3004 AN: 5694

European-Non Finnish (NFE) AF: 0.538 AC: 579821 AN: 1077918

Other (OTH) AF: 0.517 AC: 29932 AN: 57940

GnomAD4 genome AF: 0.500 AC: 75951 AN: 151958 Hom.: 19133 Cov.: 33 AF XY: 0.498 AC XY: 36995 AN XY: 74268

African (AFR) AF: 0.437 AC: 18124 AN: 41456

American (AMR) AF: 0.508 AC: 7728 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2804 AN: 5162

South Asian (SAS) AF: 0.514 AC: 2479 AN: 4820

European-Finnish (FIN) AF: 0.488 AC: 5156 AN: 10560

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36194 AN: 67960

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.524 Hom.: 45556

Bravo AF: 0.498

TwinsUK AF: 0.545 AC: 2021

ALSPAC AF: 0.550 AC: 2121

ESP6500AA AF: 0.419 AC: 580

ESP6500EA AF: 0.529 AC: 1683

ExAC AF: 0.488 AC: 10469

Asia WGS AF: 0.464 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.5
DANN	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.085	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.11	B
Vest4		0.041
MPC		0.011
ClinPred		0.012	T
GERP RS		-1.4
gMVP		0.57
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: rs7113279; hg19: chr11-62863518; COSMIC: COSV70300976;