15-84888833-A-G

Variant names:

• chr15-84888833-A-G
• NM_004213.5:c.158A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004213.5(SLC28A1):​c.158A>G​(p.Glu53Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056294978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.158A>G	p.Glu53Gly	missense_variant	Exon 4 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.158A>G	p.Glu53Gly	missense_variant	Exon 4 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.158A>G	p.Glu53Gly	missense_variant	Exon 3 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000338602.6	c.158A>G	p.Glu53Gly	missense_variant	Exon 4 of 7	1		ENSP00000341629.2
SLC28A1	ENST00000538177.5	c.158A>G	p.Glu53Gly	missense_variant	Exon 3 of 15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158A>G (p.E53G) alteration is located in exon 4 (coding exon 2) of the SLC28A1 gene. This alteration results from a A to G substitution at nucleotide position 158, causing the glutamic acid (E) at amino acid position 53 to be replaced by a glycine (G). 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	Benign	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.73
DEOGEN2	Benign	0.015	.;T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.55	T;T;T;.
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L;.;L;L
PhyloP100		1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.46	N;N;N;N
REVEL	Benign	0.026
Sift	Benign	0.30	T;T;T;T
Sift4G	Uncertain	0.037	D;T;T;T
Polyphen		0.052	B;B;B;B
Vest4		0.083
MutPred		0.13		Gain of MoRF binding (P = 0.0424);Gain of MoRF binding (P = 0.0424);Gain of MoRF binding (P = 0.0424);Gain of MoRF binding (P = 0.0424);
MVP		0.29
MPC		0.12
ClinPred		0.10	T
GERP RS		0.98
Varity_R		0.044
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr15-85432064;