11-63083267-G-C

Position:

• chr11-63083267-G-C

Variant summary

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

The NM_001136506.2(SLC22A24):​c.1261C>G​(p.Leu421Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A24 NM_001136506.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.18

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=0.31304657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A24	NM_001136506.2	c.1261C>G	p.Leu421Val	missense_variant	7/10	ENST00000612278.4	NP_001129978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A24	ENST00000612278.4	c.1261C>G	p.Leu421Val	missense_variant	7/10	5	NM_001136506.2	ENSP00000480336	P4
SLC22A24	ENST00000417740.5	c.1261C>G	p.Leu421Val	missense_variant	7/10	5		ENSP00000396586	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.1261C>G (p.L421V) alteration is located in exon 7 (coding exon 7) of the SLC22A24 gene. This alteration results from a C to G substitution at nucleotide position 1261, causing the leucine (L) at amino acid position 421 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.1
DANN	Uncertain	1.0
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.63	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.014	D;.
Sift4G	Uncertain	0.025	D;D
Polyphen		0.99	D;.
Vest4		0.17
MutPred		0.61		Gain of catalytic residue at L421 (P = 0.0414);Gain of catalytic residue at L421 (P = 0.0414);
MVP		0.48
MPC		0.025
ClinPred		0.61	D
GERP RS		-0.69
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62850739;