11-63096046-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136506.2(SLC22A24):​c.1015T>A​(p.Ser339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,590 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35157883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A24	NM_001136506.2	c.1015T>A	p.Ser339Thr	missense_variant	Exon 6 of 10	ENST00000612278.4	NP_001129978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4	c.1015T>A	p.Ser339Thr	missense_variant	Exon 6 of 10	5	NM_001136506.2	ENSP00000480336.1
SLC22A24	ENST00000417740.5	c.1015T>A	p.Ser339Thr	missense_variant	Exon 6 of 10	5		ENSP00000396586.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000651 AC: 1 AN: 153562 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81466

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000406

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1398590 Hom.: 0 Cov.: 41 AF XY: 0.00000290 AC XY: 2 AN XY: 689816

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.043
DANN	Benign	0.71
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.15
Sift	Benign	0.22	T;.
Sift4G	Benign	0.14	T;T
Polyphen		0.025	B;.
Vest4		0.15
MutPred		0.44		Gain of phosphorylation at T335 (P = 0.1222);Gain of phosphorylation at T335 (P = 0.1222);
MVP		0.23
MPC		0.011
ClinPred		0.025	T
GERP RS		-1.4
gMVP		0.15

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: rs7113279; hg19: chr11-62863518;