15-84935498-G-T

Variant summary

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

The NM_004213.5(SLC28A1):c.1561G>T(p.Asp521Tyr) 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. 13/21 in silico tools predict 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. D521N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18253875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.1561G>T	p.Asp521Tyr	missense_variant	15/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.1561G>T	p.Asp521Tyr	missense_variant	15/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.1561G>T	p.Asp521Tyr	missense_variant	14/18	1		P1
SLC28A1	ENST00000538177.5	c.1084-7947G>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.076	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.049
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.95	P;P
Vest4		0.24
MutPred		0.47		Gain of MoRF binding (P = 0.0365);Gain of MoRF binding (P = 0.0365);
MVP		0.38
MPC		0.29
ClinPred		0.63	D
GERP RS		-0.14
Varity_R		0.18
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs2242046; hg19: chr15-85478729;