NM_199352.6:c.1529T>C

Variant names:

• chr11-63163939-A-G
• rs1365263685
• NM_199352.6:c.1529T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199352.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A25	NM_199352.6	MANE Select	c.1529T>C	p.Leu510Pro	missense	Exon 12 of 12	NP_955384.3	Q6T423

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A25	ENST00000306494.11	TSL:1 MANE Select	c.1529T>C	p.Leu510Pro	missense	Exon 12 of 12	ENSP00000307443.6	Q6T423
	SLC22A25	ENST00000525295.1	TSL:1	n.*782T>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000435614.1	E9PJ86
	SLC22A25	ENST00000527057.5	TSL:1	n.*478T>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000432242.1	H0YCS4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.9
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
Mutation Taster		=99/1	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

dbSNP: rs1365263685; hg19: chr11-62931411;