Variant 15-84904159-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000394573.6(SLC28A1):c.524G>A(p.Arg175Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SLC28A1
ENST00000394573.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12819377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	7/19	ENST00000394573.6	NP_004204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	7/19	1	NM_004213.5	ENSP00000378074	P1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	6/18	1		ENSP00000286749	P1	O00337-1
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.524G>A	p.Arg175Gln	missense_variant	6/15	2		ENSP00000443752

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251452

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

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

Apr 16, 2024

The c.524G>A (p.R175Q) alteration is located in exon 7 (coding exon 5) of the SLC28A1 gene. This alteration results from a G to A substitution at nucleotide position 524, causing the arginine (R) at amino acid position 175 to be replaced by a glutamine (Q). 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

0.085

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Benign

0.010

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

.;M;M

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.98

D;P;P

Vest4

0.23

MutPred

0.28

Gain of disorder (P = 0.1074);Gain of disorder (P = 0.1074);Gain of disorder (P = 0.1074);

MVP

0.53

MPC

0.12

ClinPred

0.18

GERP RS

3.5

Varity_R

0.11

gMVP

0.42

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