SLC28A2 p.Ser75Arg

Variant names:

• chr15-45262067-A-C
• NM_004212.4:c.223A>C
• SLC28A2 p.Ser75Arg

Your query was ambiguous. Multiple possible variants found:

• chr15-45262067-A-C
• chr15-45262069-C-A
• chr15-45262069-C-G
• chr15-45262067-AGC-CGT
• chr15-45262067-AGC-CGA
• chr15-45262067-AGC-CGG

Variant summary

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

The NM_004212.4(SLC28A2):​c.223A>C​(p.Ser75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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: 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=0.05284369).

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.223A>C	p.Ser75Arg	missense	Exon 4 of 18	NP_004203.2	O43868
	SLC28A2-AS1	NR_120335.1		n.27-6069T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A2	ENST00000347644.8	TSL:1 MANE Select	c.223A>C	p.Ser75Arg	missense	Exon 4 of 18	ENSP00000315006.4	O43868
	SLC28A2	ENST00000959719.1		c.223A>C	p.Ser75Arg	missense	Exon 4 of 18	ENSP00000629778.1
	SLC28A2	ENST00000959720.1		c.223A>C	p.Ser75Arg	missense	Exon 4 of 17	ENSP00000629779.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.9
DANN	Benign	0.91
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.26	N
PhyloP100		-0.086
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.28	N
REVEL	Uncertain	0.35
Sift	Benign	0.56	T
Sift4G	Benign	0.50	T
Varity_R		0.043
gMVP		0.13
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-45554265;