chr9-84288152-C-T

Variant names:

• chr9-84288152-C-T
• rs75984623
• NM_001199633.2:c.1176G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001199633.2(SLC28A3):​c.1176G>A​(p.Ala392Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,006 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (27 hom.)
• Consequence: SLC28A3 NM_001199633.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.891
• Publications: 2 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=-0.78).
• BP6: Variant 9-84288152-C-T is Benign according to our data. Variant chr9-84288152-C-T is described in ClinVar as Benign. ClinVar VariationId is 768311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.891 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1661/152238) while in subpopulation AFR AF = 0.0383 (1590/41540). AF 95% confidence interval is 0.0367. There are 33 homozygotes in GnomAd4. There are 806 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199633.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A3	NM_001199633.2	MANE Select	c.1176G>A	p.Ala392Ala	synonymous	Exon 12 of 18	NP_001186562.1	Q9HAS3-1
	SLC28A3	NM_022127.3		c.1176G>A	p.Ala392Ala	synonymous	Exon 13 of 19	NP_071410.1	Q9HAS3-1
	SLC28A3	NR_037638.3		n.1477G>A		non_coding_transcript_exon	Exon 13 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A3	ENST00000376238.5	TSL:1 MANE Select	c.1176G>A	p.Ala392Ala	synonymous	Exon 12 of 18	ENSP00000365413.4	Q9HAS3-1
	SLC28A3-AS1	ENST00000419815.1	TSL:3	n.182-1788C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1649 AN: 152120 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00295 AC: 741 AN: 251280 AF XY: 0.00219

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00116 AC: 1701 AN: 1461768 Hom.: 27 Cov.: 31 AF XY: 0.00100 AC XY: 730 AN XY: 727188

African (AFR) AF: 0.0399 AC: 1336 AN: 33478

American (AMR) AF: 0.00192 AC: 86 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111922

Other (OTH) AF: 0.00272 AC: 164 AN: 60384

GnomAD4 genome AF: 0.0109 AC: 1661 AN: 152238 Hom.: 33 Cov.: 32 AF XY: 0.0108 AC XY: 806 AN XY: 74438

African (AFR) AF: 0.0383 AC: 1590 AN: 41540

American (AMR) AF: 0.00301 AC: 46 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00467 Hom.: 22

Bravo AF: 0.0125

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.60
DANN	Benign	0.62
PhyloP100		-0.89
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75984623; hg19: chr9-86903067; COSMIC: COSV66152663;