rs17215633

chr15-45267576-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0083 (27 hom., cov: 31)
  • Exomes 𝑓: 0.00081 (22 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85

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

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A2	NM_004212.4	c.1064T>C	p.Phe355Ser	missense_variant	11/18	ENST00000347644.8
SLC28A2-AS1	NR_120335.1	n.27-11578A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A2	ENST00000347644.8	c.1064T>C	p.Phe355Ser	missense_variant	11/18	1	NM_004212.4	P1
SLC28A2-AS1	ENST00000663463.1	n.55+11621A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1263 AN: 152076 Hom.: 27 Cov.: 31

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.: 8 AF XY: 0.00132 AC XY: 179 AN XY: 135874

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.: 22 Cov.: 32 AF XY: 0.000686 AC XY: 499 AN XY: 727238

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.: 27 Cov.: 31 AF XY: 0.00800 AC XY: 595 AN XY: 74400

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.: 9

Bravo AF: 0.00940

ESP6500AA AF: 0.0296 AC: 130

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00246 AC: 299

Asia WGS AF: 0.000866 AC: 3 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	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.9	H
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.77
MVP		0.30
MPC		0.12
ClinPred		0.14	T
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

Other links and lift over

dbSNP: rs17215633; hg19: chr15-45559774; COSMIC: COSV99052802; COSMIC: COSV99052802;