11-63163903-G-C

Position:

• chr11-63163903-G-C

Variant summary

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

The NM_199352.6(SLC22A25):​c.1565C>G​(p.Pro522Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

Genes affected

SLC22A25 (HGNC:32935): (solute carrier family 22 member 25) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [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
SLC22A25	NM_199352.6	c.1565C>G	p.Pro522Arg	missense_variant	12/12	ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.1565C>G	p.Pro522Arg	missense_variant	12/12	1	NM_199352.6	ENSP00000307443.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461706 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727150

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Nov 23, 2024

The c.1565C>G (p.P522R) alteration is located in exon 9 (coding exon 9) of the SLC22A25 gene. This alteration results from a C to G substitution at nucleotide position 1565, causing the proline (P) at amino acid position 522 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.41		Loss of catalytic residue at N520 (P = 0.0895);
MVP		0.53
MPC		0.11
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.57
gMVP		0.48

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: chr11-62931375;