Variant 15-84888842-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004213.5(SLC28A1):c.167C>G(p.Pro56Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P56L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

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: 0.0900

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06376156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.167C>G	p.Pro56Arg	missense_variant	4/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.167C>G	p.Pro56Arg	missense_variant	4/19	1	NM_004213.5	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.167C>G	p.Pro56Arg	missense_variant	3/18	1		P1	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.167C>G	p.Pro56Arg	missense_variant	4/7	1			O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.167C>G	p.Pro56Arg	missense_variant	3/15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1400256

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690840

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.167C>G (p.P56R) alteration is located in exon 4 (coding exon 2) of the SLC28A1 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the proline (P) at amino acid position 56 to be replaced by an arginine (R). 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

0.070

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.4

DANN

Benign

0.29

DEOGEN2

Benign

0.0075

.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.57

T;T;T;.

M_CAP

Benign

0.0050

MetaRNN

Benign

0.064

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.88

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.52

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.14

B;B;B;B

Vest4

0.091

MutPred

0.24

Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);Gain of MoRF binding (P = 0.0056);

MVP

0.22

MPC

0.082

ClinPred

0.069

GERP RS

0.13

Varity_R

0.025

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over