11-63163939-A-G

Position:

• chr11-63163939-A-G

Variant summary

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

The NM_199352.6(SLC22A25):​c.1529T>C​(p.Leu510Pro) 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. 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: 32)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39622632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.1529T>C	p.Leu510Pro	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.1529T>C	p.Leu510Pro	missense_variant	12/12	1	NM_199352.6	ENSP00000307443.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Sep 13, 2023

The c.1529T>C (p.L510P) alteration is located in exon 9 (coding exon 9) of the SLC22A25 gene. This alteration results from a T to C substitution at nucleotide position 1529, causing the leucine (L) at amino acid position 510 to be replaced by a proline (P). 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	0.21
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.16
Sift	Benign	0.048	D
Sift4G	Uncertain	0.018	D
Polyphen		0.16	B
Vest4		0.30
MutPred		0.77		Loss of stability (P = 0.0222);
MVP		0.39
MPC		0.017
ClinPred		0.82	D
GERP RS		2.4
Varity_R		0.71
gMVP		0.65

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: chr11-62931411;