chr6-3285097-T-A

Position:

• chr6-3285097-T-A

Variant summary

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

The NM_015482.2(SLC22A23):​c.1561A>T​(p.Ser521Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC22A23 NM_015482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07

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]

PSMG4 (HGNC:21108): (proteasome assembly chaperone 4) Predicted to be involved in proteasome assembly. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A23	NM_015482.2	c.1561A>T	p.Ser521Cys	missense_variant	8/10	ENST00000406686.8	NP_056297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A23	ENST00000406686.8	c.1561A>T	p.Ser521Cys	missense_variant	8/10	5	NM_015482.2	ENSP00000385028	P2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

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

Feb 02, 2024

The c.1561A>T (p.S521C) alteration is located in exon 8 (coding exon 8) of the SLC22A23 gene. This alteration results from a A to T substitution at nucleotide position 1561, causing the serine (S) at amino acid position 521 to be replaced by a cysteine (C). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T;.;.;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;.;D;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.3	.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.063	T;T;T;T;T;T
Sift4G	Uncertain	0.010	D;D;D;D;D;.
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.68
MutPred		0.60		Loss of disorder (P = 8e-04);Loss of disorder (P = 8e-04);.;.;.;.;
MVP		0.77
MPC		1.0
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-3285331;