15-45263945-C-G

Position:

• chr15-45263945-C-G

Variant summary

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

The NM_004212.4(SLC28A2):​c.511C>G​(p.Pro171Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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:):

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	Protein	UniProt
SLC28A2	NM_004212.4	c.511C>G	p.Pro171Ala	missense_variant	6/18	ENST00000347644.8	NP_004203.2
SLC28A2-AS1	NR_120335.1	n.27-7947G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A2	ENST00000347644.8	c.511C>G	p.Pro171Ala	missense_variant	6/18	1	NM_004212.4	ENSP00000315006.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Aug 12, 2024

The c.511C>G (p.P171A) alteration is located in exon 6 (coding exon 5) of the SLC28A2 gene. This alteration results from a C to G substitution at nucleotide position 511, causing the proline (P) at amino acid position 171 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	0.11
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.20
Sift	Benign	0.085	T;D
Sift4G	Benign	0.19	T;D
Polyphen		1.0	D;.
Vest4		0.43
MutPred		0.52		Gain of helix (P = 0.0128);.;
MVP		0.76
MPC		0.29
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45556143;