chr9-84279364-A-G

Variant names:

• chr9-84279364-A-G
• rs760332361
• NM_001199633.2:c.1850T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199633.2(SLC28A3):​c.1850T>C​(p.Val617Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,610,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC28A3 NM_001199633.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0830
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033338815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A3	NM_001199633.2	c.1850T>C	p.Val617Ala	missense_variant	Exon 17 of 18	ENST00000376238.5	NP_001186562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC28A3	ENST00000376238.5	c.1850T>C	p.Val617Ala	missense_variant	Exon 17 of 18	1	NM_001199633.2	ENSP00000365413.4
SLC28A3-AS1	ENST00000419815.1	n.181+965A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249574 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1458104 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 725298

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.00 AC: 0 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.00 AC: 0 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1110016

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1850T>C (p.V617A) alteration is located in exon 18 (coding exon 17) of the SLC28A3 gene. This alteration results from a T to C substitution at nucleotide position 1850, causing the valine (V) at amino acid position 617 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.70
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.083
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.027	B
Vest4		0.15
MutPred		0.32		Loss of helix (P = 0.079);
MVP		0.014
MPC		0.22
ClinPred		0.034	T
GERP RS		-2.5
Varity_R		0.033
gMVP		0.34
Mutation Taster		=89/11	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: rs760332361; hg19: chr9-86894279;