Genetic Variant NM_004213.5:c.386A>C (chr15-84895048-A-C) – ACMG Classification: Uncertain_significance (2 pts)

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Variant links:

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]

SLC28A1 links:

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ACMG classification

Classification made for transcript

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 link	c.386A>C	p.Lys129Thr	missense_variant	Exon 6 of 19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.386A>C	p.Lys129Thr	missense_variant	Exon 6 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.386A>C	p.Lys129Thr	missense_variant	Exon 5 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.386A>C	p.Lys129Thr	missense_variant	Exon 6 of 7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.386A>C	p.Lys129Thr	missense_variant	Exon 5 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;T;T

Eigen

Benign

0.010

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.80

T;T;T;.

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

0.026

MutationAssessor

Pathogenic

3.1

M;.;M;M

PrimateAI

Benign

0.44

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over