Genetic Variant NM_004212.4:c.1064T>C (chr15-45267576-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004212.4(SLC28A2):c.1064T>C(p.Phe355Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00151 in 1,614,068 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0083 ( 27 hom., cov: 31)

Exomes 𝑓: 0.00081 ( 22 hom. )

Consequence

SLC28A2
NM_004212.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.85

Variant links:

Genes affected

SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A2 links:

SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

SLC28A2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013906479).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00831 (1264/152194) while in subpopulation AFR AF= 0.0296 (1227/41506). AF 95% confidence interval is 0.0282. There are 27 homozygotes in gnomad4. There are 595 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A2	NM_004212.4 link	c.1064T>C	p.Phe355Ser	missense_variant	Exon 11 of 18	ENST00000347644.8	NP_004203.2	O43868Q2M2A7Q53H72
SLC28A2-AS1	NR_120335.1 link	n.27-11578A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A2	ENST00000347644.8 link	c.1064T>C	p.Phe355Ser	missense_variant	Exon 11 of 18	1	NM_004212.4	ENSP00000315006.4		O43868

Frequencies

GnomAD3 genomes

AF:

0.00831

AC:

1263

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00192

AC:

482

AN:

251420

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000806

AC:

1178

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

499

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0315

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00831

AC:

1264

AN:

152194

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

595

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00940

ESP6500AA

AF:

0.0296

AC:

130

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00246

AC:

299

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.9

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.77

MVP

0.30

MPC

0.12

ClinPred

0.14

GERP RS

5.8

Varity_R

0.94

gMVP

0.93

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over