Genetic Variant NM_004213.5:c.167C>G (chr15-84888842-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC28A1	NM_004213.5	MANE Select	c.167C>G	p.Pro56Arg	missense	Exon 4 of 19	NP_004204.3
SLC28A1	NM_001287762.2		c.167C>G	p.Pro56Arg	missense	Exon 3 of 18	NP_001274691.1	O00337-1
SLC28A1	NM_001321722.2		c.167C>G	p.Pro56Arg	missense	Exon 4 of 19	NP_001308651.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.167C>G	p.Pro56Arg	missense	Exon 4 of 19	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3	TSL:1	c.167C>G	p.Pro56Arg	missense	Exon 3 of 18	ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6	TSL:1	c.167C>G	p.Pro56Arg	missense	Exon 4 of 7	ENSP00000341629.2	O00337-2

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

African (AFR)

AF:

0.00

AC:

AN:

31662

American (AMR)

AF:

0.00

AC:

AN:

35868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

35834

South Asian (SAS)

AF:

0.00

AC:

AN:

79256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1079434

Other (OTH)

AF:

0.0000172

AC:

AN:

58038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.4

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0075

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.57

M_CAP

Benign

0.0050

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.090

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.88

REVEL

Benign

0.14

Sift

Benign

0.52

Sift4G

Benign

0.68

Polyphen

0.14

Vest4

0.091

MutPred

0.24

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

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over