6-3410302-T-C

Variant summary

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

The NM_015482.2(SLC22A23):c.799A>G(p.Ile267Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC22A23 NM_015482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

SLC22A23 (HGNC:21106): (solute carrier family 22 member 23) SLC22A23 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=0.18809873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A23	NM_015482.2	c.799A>G	p.Ile267Val	missense_variant	3/10	ENST00000406686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A23	ENST00000406686.8	c.799A>G	p.Ile267Val	missense_variant	3/10	5	NM_015482.2	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250214 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

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: 0.00000883

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461246 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726886

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000594

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 20, 2021

The c.799A>G (p.I267V) alteration is located in exon 3 (coding exon 3) of the SLC22A23 gene. This alteration results from a A to G substitution at nucleotide position 799, causing the isoleucine (I) at amino acid position 267 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	0.090
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	21
Dann	Benign	0.74
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;T;D;D;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.090	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;.;T
Polyphen		0.19	B;B;.;.;.
Vest4		0.27
MutPred		0.62		Gain of catalytic residue at I267 (P = 0.0207);Gain of catalytic residue at I267 (P = 0.0207);.;.;Gain of catalytic residue at I267 (P = 0.0207);
MVP		0.33
MPC		0.28
ClinPred		0.086	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.32

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: rs1327218910; hg19: chr6-3410536;