1-115976676-C-G

Variant names:

• chr1-115976676-C-G
• NM_018420.3:c.49C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018420.3(SLC22A15):​c.49C>G​(p.Gln17Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A15 NM_018420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46
• Publications: 0 publications found

Genes affected

SLC22A15 (HGNC:20301): (solute carrier family 22 member 15) Organic ion transporters, such as SLC22A15, transport various medically and physiologically important compounds, including pharmaceuticals, toxins, hormones, neurotransmitters, and cellular metabolites. These transporters are also referred to as amphiphilic solute facilitators (ASFs).[supplied by OMIM, Apr 2004]

ENSG00000303689 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A15	NM_018420.3	c.49C>G	p.Gln17Glu	missense_variant	Exon 1 of 12	ENST00000369503.9	NP_060890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A15	ENST00000369503.9	c.49C>G	p.Gln17Glu	missense_variant	Exon 1 of 12	1	NM_018420.3	ENSP00000358515.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.49C>G (p.Q17E) alteration is located in exon 1 (coding exon 1) of the SLC22A15 gene. This alteration results from a C to G substitution at nucleotide position 49, causing the glutamine (Q) at amino acid position 17 to be replaced by a glutamic acid (E). 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	-0.077	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.91	P;D
Vest4		0.68
MutPred		0.70		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.80
MPC		0.31
ClinPred		0.97	D
GERP RS		3.2
PromoterAI		0.11	Neutral
Varity_R		0.72
gMVP		0.69
Mutation Taster		=89/11	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: chr1-116519297;