15-45262069-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004212.4(SLC28A2):c.225C>A(p.Ser75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,610,694 control chromosomes in the GnomAD database, including 308,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (20716 hom., cov: 31)
  • Exomes 𝑓: 0.61 (287307 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.6951517E-6).
• BP6: Variant 15-45262069-C-A is Benign according to our data. Variant chr15-45262069-C-A is described in ClinVar as [Benign]. Clinvar id is 1267759.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A2	NM_004212.4	c.225C>A	p.Ser75Arg	missense_variant	4/18	ENST00000347644.8
SLC28A2-AS1	NR_120335.1	n.27-6071G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A2	ENST00000347644.8	c.225C>A	p.Ser75Arg	missense_variant	4/18	1	NM_004212.4	P1
SLC28A2-AS1	ENST00000663463.1	n.55+17128G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71905 AN: 151958 Hom.: 20722 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.490

GnomAD3 exomes AF: 0.501 AC: 125660 AN: 251060 Hom.: 36498 AF XY: 0.518 AC XY: 70311 AN XY: 135670

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.584

Gnomad EAS exome AF: 0.0855

Gnomad SAS exome AF: 0.478

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.653

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.611 AC: 890706 AN: 1458618 Hom.: 287307 Cov.: 34 AF XY: 0.610 AC XY: 442642 AN XY: 725744

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.0665

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.473 AC: 71898 AN: 152076 Hom.: 20716 Cov.: 31 AF XY: 0.464 AC XY: 34527 AN XY: 74344

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.0956

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.485

Alfa AF: 0.598 Hom.: 36752

Bravo AF: 0.443

TwinsUK AF: 0.672 AC: 2493

ALSPAC AF: 0.663 AC: 2555

ESP6500AA AF: 0.196 AC: 861

ESP6500EA AF: 0.665 AC: 5714

ExAC AF: 0.502 AC: 60912

Asia WGS AF: 0.279 AC: 971 AN: 3478

EpiCase AF: 0.654

EpiControl AF: 0.651

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 18, 2019

This variant is associated with the following publications: (PMID: 30315176) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	0.21
Dann	Benign	0.87
DEOGEN2	Benign	0.0067	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.11	T;T
MetaRNN	Benign	0.0000057	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.26	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.28	N;N
REVEL	Uncertain	0.35
Sift	Benign	0.56	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0	B;.
Vest4		0.050
MutPred		0.16		Gain of MoRF binding (P = 0.0107);.;
MPC		0.044
ClinPred		0.0013	T
GERP RS		-3.7
Varity_R		0.052
gMVP		0.13

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: rs1060896; hg19: chr15-45554267; COSMIC: COSV61665205; COSMIC: COSV61665205;