1-115976674-A-T

Variant names:

• chr1-115976674-A-T
• rs748679951
• NM_018420.3:c.47A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018420.3(SLC22A15):​c.47A>T​(p.Tyr16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. Y16S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC22A15 NM_018420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4012026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A15	NM_018420.3	c.47A>T	p.Tyr16Phe	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.47A>T	p.Tyr16Phe	missense_variant	Exon 1 of 12	1	NM_018420.3	ENSP00000358515.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435086 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714162

African (AFR) AF: 0.00 AC: 0 AN: 31082

American (AMR) AF: 0.00 AC: 0 AN: 42344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25452

East Asian (EAS) AF: 0.00 AC: 0 AN: 36948

South Asian (SAS) AF: 0.00 AC: 0 AN: 84086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100356

Other (OTH) AF: 0.00 AC: 0 AN: 59258

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	0.0022	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		2.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.27	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.013	B;B
Vest4		0.41
MutPred		0.76		Loss of loop (P = 0.3664);Loss of loop (P = 0.3664);
MVP		0.40
MPC		0.20
ClinPred		0.68	D
GERP RS		4.0
PromoterAI		-0.075	Neutral
Varity_R		0.33
gMVP		0.19
Mutation Taster		=94/6	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: rs748679951; hg19: chr1-116519295;