rs7853758

Variant names:

• chr9-84286011-G-A
• rs7853758
• NM_001199633.2:c.1381C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-84286011-G-A
• chr9-84286011-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001199633.2(SLC28A3):​c.1381C>T​(p.Leu461Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,680 control chromosomes in the GnomAD database, including 19,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3142 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16505 hom.)
• Consequence: SLC28A3 NM_001199633.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.773
• Publications: 113 publications found

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]

SLC28A3-AS1 (HGNC:55460): (SLC28A3 regulatory antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-84286011-G-A is Benign according to our data. Variant chr9-84286011-G-A is described in ClinVar as [Benign]. Clinvar id is 375669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.773 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.1381C>T	p.Leu461Leu	synonymous_variant	Exon 13 of 18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.1381C>T	p.Leu461Leu	synonymous_variant	Exon 13 of 18	1	NM_001199633.2	ENSP00000365413.4
SLC28A3-AS1	ENST00000419815.1	n.182-3929G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28410 AN: 152030 Hom.: 3136 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.153 AC: 38437 AN: 250790 AF XY: 0.147

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.151

Gnomad FIN exome AF: 0.0663

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.145 AC: 211832 AN: 1461532 Hom.: 16505 Cov.: 33 AF XY: 0.144 AC XY: 104536 AN XY: 727050

African (AFR) AF: 0.322 AC: 10792 AN: 33470

American (AMR) AF: 0.201 AC: 8965 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5632 AN: 26130

East Asian (EAS) AF: 0.116 AC: 4597 AN: 39692

South Asian (SAS) AF: 0.128 AC: 11079 AN: 86220

European-Finnish (FIN) AF: 0.0702 AC: 3750 AN: 53410

Middle Eastern (MID) AF: 0.152 AC: 874 AN: 5766

European-Non Finnish (NFE) AF: 0.140 AC: 156101 AN: 1111786

Other (OTH) AF: 0.166 AC: 10042 AN: 60384

GnomAD4 genome AF: 0.187 AC: 28460 AN: 152148 Hom.: 3142 Cov.: 32 AF XY: 0.180 AC XY: 13410 AN XY: 74412

African (AFR) AF: 0.308 AC: 12770 AN: 41458

American (AMR) AF: 0.188 AC: 2868 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3470

East Asian (EAS) AF: 0.149 AC: 770 AN: 5184

South Asian (SAS) AF: 0.132 AC: 638 AN: 4826

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10608

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9505 AN: 67996

Other (OTH) AF: 0.190 AC: 401 AN: 2114

Alfa AF: 0.161 Hom.: 8578

Bravo AF: 0.203

Asia WGS AF: 0.163 AC: 568 AN: 3478

EpiCase AF: 0.144

EpiControl AF: 0.143

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs7853758; hg19: chr9-86900926; COSMIC: COSV66153362;