9-84290181-G-A

Variant names:

• chr9-84290181-G-A
• rs7043492
• NM_001199633.2:c.1122C>T

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.1122C>T​(p.Ser374Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,086 control chromosomes in the GnomAD database, including 57 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: 33)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: SLC28A3 NM_001199633.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0980
• Publications: 5 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=-0.49).
• BP6: Variant 9-84290181-G-A is Benign according to our data. Variant chr9-84290181-G-A is described in ClinVar as Benign. ClinVar VariationId is 768312.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.098 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1655/152276) while in subpopulation AFR AF = 0.0382 (1585/41544). AF 95% confidence interval is 0.0366. There are 33 homozygotes in GnomAd4. There are 801 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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.1122C>T	p.Ser374Ser	synonymous	Exon 11 of 18	NP_001186562.1	Q9HAS3-1
	SLC28A3	NM_022127.3		c.1122C>T	p.Ser374Ser	synonymous	Exon 12 of 19	NP_071410.1	Q9HAS3-1
	SLC28A3	NR_037638.3		n.1423C>T		non_coding_transcript_exon	Exon 12 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A3	ENST00000376238.5	TSL:1 MANE Select	c.1122C>T	p.Ser374Ser	synonymous	Exon 11 of 18	ENSP00000365413.4	Q9HAS3-1
	SLC28A3-AS1	ENST00000419815.1	TSL:3	n.*50G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1643 AN: 152158 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0380

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: 0.00672

GnomAD2 exomes AF: 0.00293 AC: 737 AN: 251344 AF XY: 0.00215

Gnomad AFR exome AF: 0.0400

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00115 AC: 1684 AN: 1461810 Hom.: 24 Cov.: 30 AF XY: 0.000991 AC XY: 721 AN XY: 727212

African (AFR) AF: 0.0399 AC: 1335 AN: 33474

American (AMR) AF: 0.00190 AC: 85 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111956

Other (OTH) AF: 0.00265 AC: 160 AN: 60388

GnomAD4 genome AF: 0.0109 AC: 1655 AN: 152276 Hom.: 33 Cov.: 33 AF XY: 0.0108 AC XY: 801 AN XY: 74444

African (AFR) AF: 0.0382 AC: 1585 AN: 41544

American (AMR) AF: 0.00301 AC: 46 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68030

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.00451 Hom.: 40

Bravo AF: 0.0125

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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	-0.49
CADD	Benign	0.56
DANN	Benign	0.87
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7043492; hg19: chr9-86905096; COSMIC: COSV66154235; COSMIC: COSV66154235;