15-84895048-A-C

Variant summary

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

The NM_004213.5(SLC28A1):c.386A>C(p.Lys129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.386A>C	p.Lys129Thr	missense_variant	6/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.386A>C	p.Lys129Thr	missense_variant	6/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.386A>C	p.Lys129Thr	missense_variant	5/18	1		P1
SLC28A1	ENST00000338602.6	c.386A>C	p.Lys129Thr	missense_variant	6/7	1
SLC28A1	ENST00000538177.5	c.386A>C	p.Lys129Thr	missense_variant	5/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461710 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727162

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.386A>C (p.K129T) alteration is located in exon 6 (coding exon 4) of the SLC28A1 gene. This alteration results from a A to C substitution at nucleotide position 386, causing the lysine (K) at amino acid position 129 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Benign	0.010
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.80	T;T;T;.
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Uncertain	0.026	D
MutationAssessor	Pathogenic	3.1	M;.;M;M
MutationTaster	Benign	0.94	D;D;D;D;D;D;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	D;T;T;T
Sift4G	Uncertain	0.010	D;T;T;T
Polyphen		1.0	D;D;P;P
Vest4		0.44
MutPred		0.40		Loss of MoRF binding (P = 0.0514);Loss of MoRF binding (P = 0.0514);Loss of MoRF binding (P = 0.0514);Loss of MoRF binding (P = 0.0514);
MVP		0.74
MPC		0.15
ClinPred		0.87	D
GERP RS		2.0
Varity_R		0.10
gMVP		0.63

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-85438279;