15-84904159-G-T

Variant names:

• chr15-84904159-G-T
• NM_004213.5:c.524G>T

Variant summary

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

The NM_004213.5(SLC28A1):​c.524G>T​(p.Arg175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.524G>T	p.Arg175Leu	missense_variant	Exon 7 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.524G>T	p.Arg175Leu	missense_variant	Exon 7 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.524G>T	p.Arg175Leu	missense_variant	Exon 6 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000538177.5	c.524G>T	p.Arg175Leu	missense_variant	Exon 6 of 15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Benign	0.68
DEOGEN2	Benign	0.083	T;T;T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Benign	0.22
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.52
MutPred		0.35		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.60
MPC		0.42
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.33
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-85447390;