NM_004212.4:c.1064T>C

Variant names:

• chr15-45267576-T-C
• rs17215633
• NM_004212.4:c.1064T>C

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004212.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	NM_004212.4	MANE Select	c.1064T>C	p.Phe355Ser	missense	Exon 11 of 18	NP_004203.2
	SLC28A2-AS1	NR_120335.1		n.27-11578A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.1064T>C	p.Phe355Ser	missense	Exon 11 of 18	ENSP00000315006.4
	SLC28A2	ENST00000559924.1	TSL:5	n.*463T>C		non_coding_transcript_exon	Exon 6 of 7	ENSP00000454046.1
	SLC28A2	ENST00000559924.1	TSL:5	n.*463T>C		3_prime_UTR	Exon 6 of 7	ENSP00000454046.1

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

GnomAD2 exomes AF: 0.00192 AC: 482 AN: 251420 AF XY: 0.00132

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 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

African (AFR) AF: 0.0315 AC: 1053 AN: 33480

American (AMR) AF: 0.000537 AC: 24 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112000

Other (OTH) AF: 0.00146 AC: 88 AN: 60396

GnomAD4 genome AF: 0.00831 AC: 1264 AN: 152194 Hom.: 27 Cov.: 31 AF XY: 0.00800 AC XY: 595 AN XY: 74400

African (AFR) AF: 0.0296 AC: 1227 AN: 41506

American (AMR) AF: 0.00177 AC: 27 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00286 Hom.: 25

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 v4.9

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
PhyloP100		4.8
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
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

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