NM_004212.4:c.554T>A

Variant names:

• chr15-45263988-T-A
• NM_004212.4:c.554T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004212.4(SLC28A2):​c.554T>A​(p.Leu185His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004212.4. 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
	SLC28A2	NM_004212.4	MANE Select	c.554T>A	p.Leu185His	missense	Exon 6 of 18	NP_004203.2	O43868
	SLC28A2-AS1	NR_120335.1		n.27-7990A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.554T>A	p.Leu185His	missense	Exon 6 of 18	ENSP00000315006.4	O43868
	SLC28A2	ENST00000959719.1		c.554T>A	p.Leu185His	missense	Exon 6 of 18	ENSP00000629778.1
	SLC28A2	ENST00000959720.1		c.554T>A	p.Leu185His	missense	Exon 6 of 17	ENSP00000629779.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		5.0
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.26
Sift	Uncertain	0.012	D
Sift4G	Benign	0.31	T
Polyphen		0.99	D
Vest4		0.64
MutPred		0.48		Loss of stability (P = 0.0239)
MVP		0.28
MPC		0.29
ClinPred		0.90	D
GERP RS		4.6
Varity_R		0.76
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr15-45556186;