rs777717825

Variant names:

• chr11-63083315-G-A
• rs777717825
• NM_001136506.2:c.1213C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-63083315-G-A
• chr11-63083315-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001136506.2(SLC22A24):​c.1213C>T​(p.Arg405Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.925

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.1213C>T	p.Arg405Cys	missense	Exon 7 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.1213C>T	p.Arg405Cys	missense	Exon 7 of 10	ENSP00000480336.1	Q8N4F4-2
	SLC22A24	ENST00000417740.5	TSL:5	c.1213C>T	p.Arg405Cys	missense	Exon 7 of 10	ENSP00000396586.1	Q8N4F4-3
	SLC22A24	ENST00000908490.1		c.519-3318C>T		intron	N/A	ENSP00000578549.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1408068 Hom.: 0 Cov.: 32 AF XY: 0.00000431 AC XY: 3 AN XY: 695294

African (AFR) AF: 0.00 AC: 0 AN: 32272

American (AMR) AF: 0.00 AC: 0 AN: 36818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25326

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36834

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083040

Other (OTH) AF: 0.00 AC: 0 AN: 58386

GnomAD4 genome Cov.: 32

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.039	N
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.13	T
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.27
Sift	Benign	0.059	T
Sift4G	Benign	0.081	T
Polyphen		0.98	D
Vest4		0.50
MutPred		0.86		Gain of catalytic residue at M403 (P = 0.0011)
MVP		0.76
MPC		0.023
ClinPred		0.83	D
GERP RS		2.9
gMVP		0.72
Mutation Taster		=100/0	polymorphism

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: rs777717825; hg19: chr11-62850787; COSMIC: COSV70300158;