1-116019685-G-T

Variant names:

• chr1-116019685-G-T
• rs371866306
• NM_018420.3:c.404G>T

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.404G>T​(p.Arg135Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R135H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A15 NM_018420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 1 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]

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, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A15	NM_018420.3	c.404G>T	p.Arg135Leu	missense_variant	Exon 3 of 12	ENST00000369503.9	NP_060890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A15	ENST00000369503.9	c.404G>T	p.Arg135Leu	missense_variant	Exon 3 of 12	1	NM_018420.3	ENSP00000358515.4
SLC22A15	ENST00000369502.1	c.404G>T	p.Arg135Leu	missense_variant	Exon 3 of 6	2		ENSP00000358514.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.8	M;M
PhyloP100		5.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.96	D;P
Vest4		0.81
MutPred		0.73		Loss of methylation at R135 (P = 0.0219);Loss of methylation at R135 (P = 0.0219);
MVP		0.82
MPC		0.91
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.63
gMVP		0.66
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371866306; hg19: chr1-116562306;