chr11-63166098-G-T

Position:

• chr11-63166098-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199352.6(SLC22A25):​c.1231C>A​(p.Leu411Ile) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A25 NM_199352.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26360974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A25	NM_199352.6	c.1231C>A	p.Leu411Ile	missense_variant	10/12	ENST00000306494.11	NP_955384.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A25	ENST00000306494.11	c.1231C>A	p.Leu411Ile	missense_variant	10/12	1	NM_199352.6	ENSP00000307443.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Oct 05, 2021

The c.1231C>A (p.L411I) alteration is located in exon 7 (coding exon 7) of the SLC22A25 gene. This alteration results from a C to A substitution at nucleotide position 1231, causing the leucine (L) at amino acid position 411 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.014
DANN	Benign	0.49
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.14
Sift	Benign	0.79	T
Sift4G	Benign	0.66	T
Polyphen		0.69	P
Vest4		0.12
MutPred		0.66		Gain of catalytic residue at L416 (P = 0.0426);
MVP		0.014
MPC		0.016
ClinPred		0.17	T
GERP RS		-9.3
Varity_R		0.072
gMVP		0.052

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

LitVar

Other links and lift over

dbSNP: rs941361673; hg19: chr11-62933570;