NM_001136506.2:c.1405G>T

Variant names:

• chr11-63081113-C-A
• rs142507239
• NM_001136506.2:c.1405G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136506.2(SLC22A24):​c.1405G>T​(p.Ala469Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,551,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.08
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036860943).

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.1405G>T	p.Ala469Ser	missense	Exon 9 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.1405G>T	p.Ala469Ser	missense	Exon 9 of 10	ENSP00000480336.1	Q8N4F4-2
	SLC22A24	ENST00000417740.5	TSL:5	c.1405G>T	p.Ala469Ser	missense	Exon 9 of 10	ENSP00000396586.1	Q8N4F4-3
	SLC22A24	ENST00000908490.1		c.519-1116G>T		intron	N/A	ENSP00000578549.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000195 AC: 3 AN: 153792 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.00000643 AC: 9 AN: 1399138 Hom.: 0 Cov.: 33 AF XY: 0.00000435 AC XY: 3 AN XY: 690100

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.0000840 AC: 3 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078748

Other (OTH) AF: 0.0000517 AC: 3 AN: 57996

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.000588 AC: 9 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.0000300 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0020
DANN	Benign	0.13
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.99	T
PhyloP100		-4.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.099
Sift	Benign	0.77	T
Sift4G	Benign	0.81	T
Polyphen		0.0030	B
Vest4		0.042
MVP		0.21
MPC		0.0071
ClinPred		0.016	T
GERP RS		-7.0
gMVP		0.29
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142507239; hg19: chr11-62848585;