Genetic Variant NM_004213.5:c.248G>C (chr15-84890505-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004213.5(SLC28A1):c.248G>C(p.Arg83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC28A1
NM_004213.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.248G>C	p.Arg83Pro	missense_variant	Exon 5 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.248G>C	p.Arg83Pro	missense_variant	Exon 5 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.248G>C	p.Arg83Pro	missense_variant	Exon 4 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.248G>C	p.Arg83Pro	missense_variant	Exon 5 of 7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.248G>C	p.Arg83Pro	missense_variant	Exon 4 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248384

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

85874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4788

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111576

Other (OTH)

AF:

0.0000166

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

.;T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.67

T;T;T;.

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.79

D;D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.9

M;.;M;M

PhyloP100

0.40

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.5

D;D;D;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.033

D;D;T;T

Polyphen

1.0

D;D;P;P

Vest4

0.80

MutPred

0.50

Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);

MVP

0.88

MPC

0.32

ClinPred

0.85

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.84

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over