11-63166076-G-C

Variant names:

• chr11-63166076-G-C
• NM_199352.6:c.1253C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199352.6(SLC22A25):​c.1253C>G​(p.Thr418Ser) 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. 17/22 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)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10678035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.1253C>G	p.Thr418Ser	missense_variant	Exon 10 of 12	ENST00000306494.11	NP_955384.3
SLC22A25	XM_047426917.1	c.*202C>G		downstream_gene_variant			XP_047282873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.1253C>G	p.Thr418Ser	missense_variant	Exon 10 of 12	1	NM_199352.6	ENSP00000307443.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1253C>G (p.T418S) alteration is located in exon 7 (coding exon 7) of the SLC22A25 gene. This alteration results from a C to G substitution at nucleotide position 1253, causing the threonine (T) at amino acid position 418 to be replaced by a serine (S). 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	0.096
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.097
DANN	Benign	0.57
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.096	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.33
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.075
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.043	D
Polyphen		0.0010	B
Vest4		0.097
MutPred		0.67		Loss of stability (P = 0.342);
MVP		0.11
MPC		0.015
ClinPred		0.26	T
GERP RS		0.84
Varity_R		0.16
gMVP		0.081
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

hg19: chr11-62933548;