11-63143607-G-T

Position:

• chr11-63143607-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136506.2(SLC22A24):​c.173C>A​(p.Thr58Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18807283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A24	NM_001136506.2	c.173C>A	p.Thr58Asn	missense_variant	1/10	ENST00000612278.4
SLC22A24	NM_173586.3	c.173C>A	p.Thr58Asn	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A24	ENST00000612278.4	c.173C>A	p.Thr58Asn	missense_variant	1/10	5	NM_001136506.2	P4
SLC22A24	ENST00000326192.5	c.173C>A	p.Thr58Asn	missense_variant	1/4	1
SLC22A24	ENST00000417740.5	c.173C>A	p.Thr58Asn	missense_variant	1/10	5		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423006 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 705896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	0.099
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.047	N
LIST_S2	Uncertain	0.92	D;D;.
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.7	D;.;D
REVEL	Benign	0.090
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0060	D;D;T
Polyphen		1.0	D;.;.
Vest4		0.058
MutPred		0.43		Loss of phosphorylation at T58 (P = 0.0777);Loss of phosphorylation at T58 (P = 0.0777);Loss of phosphorylation at T58 (P = 0.0777);
MVP		0.28
MPC		0.011
ClinPred		0.97	D
GERP RS		2.3
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: rs1939748; hg19: chr11-62911079;