15-45263985-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004212.4(SLC28A2):c.551T>A(p.Ile184Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

Genes affected

SLC28A2 (HGNC:11002): (solute carrier family 28 member 2) Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in several processes, including nucleoside transport; purine nucleobase transmembrane transport; and pyrimidine-containing compound transmembrane transport. Predicted to be located in membrane. Predicted to be part of brush border membrane; coated vesicle; and vesicle membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC28A2-AS1 (HGNC:55417): (SLC28A2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A2	NM_004212.4	c.551T>A	p.Ile184Asn	missense_variant	6/18	ENST00000347644.8
SLC28A2-AS1	NR_120335.1	n.27-7987A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A2	ENST00000347644.8	c.551T>A	p.Ile184Asn	missense_variant	6/18	1	NM_004212.4	P1
SLC28A2-AS1	ENST00000663463.1	n.55+15212A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461214 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.551T>A (p.I184N) alteration is located in exon 6 (coding exon 5) of the SLC28A2 gene. This alteration results from a T to A substitution at nucleotide position 551, causing the isoleucine (I) at amino acid position 184 to be replaced by an asparagine (N). 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	0.30
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.7	H;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.93	P;.
Vest4		0.48
MutPred		0.57		Gain of catalytic residue at I184 (P = 0.0182);.;
MVP		0.45
MPC		0.30
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.68
gMVP		0.80

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: rs1567058947; hg19: chr15-45556183;