Variant chr15-84890447-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004213.5(SLC28A1):c.190A>G(p.Asn64Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,455,592 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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:

SLC28A1 (HGNC:):

SLC28A1 links:

Genome browser will be placed here

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=0.12770301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A1	NM_004213.5 linkuse as main transcript	c.190A>G	p.Asn64Asp	missense_variant	5/19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 linkuse as main transcript	c.190A>G	p.Asn64Asp	missense_variant	5/19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 linkuse as main transcript	c.190A>G	p.Asn64Asp	missense_variant	4/18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 linkuse as main transcript	c.190A>G	p.Asn64Asp	missense_variant	5/7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 linkuse as main transcript	c.190A>G	p.Asn64Asp	missense_variant	4/15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

243914

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000500

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1455592

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723782

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:

0.0000957

Gnomad4 NFE exome

AF:

0.00000360

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.190A>G (p.N64D) alteration is located in exon 5 (coding exon 3) of the SLC28A1 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the asparagine (N) at amino acid position 64 to be replaced by an aspartic acid (D). 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

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.014

.;T;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.62

T;T;T;.

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

L;.;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.26

B;B;B;B

Vest4

0.27

MutPred

0.23

Loss of MoRF binding (P = 0.0708);Loss of MoRF binding (P = 0.0708);Loss of MoRF binding (P = 0.0708);Loss of MoRF binding (P = 0.0708);

MVP

0.81

MPC

0.091

ClinPred

0.092

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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