chr15-84887832-G-T

Variant names:

• chr15-84887832-G-T
• rs1003901425
• NM_004213.5:c.72G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004213.5(SLC28A1):​c.72G>T​(p.Met24Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M24L) has been classified 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: 0.991
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07315123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5	c.72G>T	p.Met24Ile	missense_variant	Exon 3 of 19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6	c.72G>T	p.Met24Ile	missense_variant	Exon 3 of 19	1	NM_004213.5	ENSP00000378074.1
SLC28A1	ENST00000286749.3	c.72G>T	p.Met24Ile	missense_variant	Exon 2 of 18	1		ENSP00000286749.3
SLC28A1	ENST00000338602.6	c.72G>T	p.Met24Ile	missense_variant	Exon 3 of 7	1		ENSP00000341629.2
SLC28A1	ENST00000538177.5	c.72G>T	p.Met24Ile	missense_variant	Exon 2 of 15	2		ENSP00000443752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.72G>T (p.M24I) alteration is located in exon 3 (coding exon 1) of the SLC28A1 gene. This alteration results from a G to T substitution at nucleotide position 72, causing the methionine (M) at amino acid position 24 to be replaced by an isoleucine (I). 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	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.72
DEOGEN2	Benign	0.0087	.;T;T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.70	T;T;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.99
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Benign	0.032
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.63	P;B;B;B
Vest4		0.25
MutPred		0.17		Gain of catalytic residue at L29 (P = 0.0607);Gain of catalytic residue at L29 (P = 0.0607);Gain of catalytic residue at L29 (P = 0.0607);Gain of catalytic residue at L29 (P = 0.0607);
MVP		0.14
MPC		0.096
ClinPred		0.25	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.24

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: rs1003901425; hg19: chr15-85431063; COSMIC: COSV99722961;