chr9-84302386-T-C

Position:

• chr9-84302386-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199633.2(SLC28A3):​c.338A>G​(p.Tyr113Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,612,632 control chromosomes in the GnomAD database, including 6,368 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 0.11 (1086 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5282 hom.)
• Consequence: SLC28A3 NM_001199633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

Genes affected

SLC28A3 (HGNC:16484): (solute carrier family 28 member 3) Nucleoside transporters, such as SLC28A3, regulate multiple cellular processes, including neurotransmission, vascular tone, adenosine concentration in the vicinity of cell surface receptors, and transport and metabolism of nucleoside drugs. SLC28A3 shows broad specificity for pyrimidine and purine nucleosides (Ritzel et al., 2001 [PubMed 11032837]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018907189).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.338A>G	p.Tyr113Cys	missense_variant	5/18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.338A>G	p.Tyr113Cys	missense_variant	5/18	1	NM_001199633.2	ENSP00000365413.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16770 AN: 152020 Hom.: 1079 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.0839 AC: 20823 AN: 248300 Hom.: 1020 AF XY: 0.0835 AC XY: 11201 AN XY: 134224

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0674

Gnomad EAS exome AF: 0.0905

Gnomad SAS exome AF: 0.0796

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.0768

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.0813 AC: 118754 AN: 1460494 Hom.: 5282 Cov.: 32 AF XY: 0.0807 AC XY: 58649 AN XY: 726478

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0389

Gnomad4 ASJ exome AF: 0.0640

Gnomad4 EAS exome AF: 0.0781

Gnomad4 SAS exome AF: 0.0776

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.0783

Gnomad4 OTH exome AF: 0.0870

GnomAD4 genome AF: 0.110 AC: 16802 AN: 152138 Hom.: 1086 Cov.: 32 AF XY: 0.110 AC XY: 8196 AN XY: 74378

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.0818

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0814 Hom.: 1155

Bravo AF: 0.108

TwinsUK AF: 0.0828 AC: 307

ALSPAC AF: 0.0786 AC: 303

ESP6500AA AF: 0.174 AC: 766

ESP6500EA AF: 0.0767 AC: 660

ExAC AF: 0.0861 AC: 10456

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.0079
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.016	D
Polyphen		0.43	B
Vest4		0.26
MPC		0.65
ClinPred		0.098	T
GERP RS		2.8
Varity_R		0.71
gMVP		0.79

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: rs10868138; hg19: chr9-86917301; COSMIC: COSV66152107; COSMIC: COSV66152107;