15-45253280-C-T

Position:

• chr15-45253280-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004212.4(SLC28A2):​c.65C>T​(p.Pro22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,236 control chromosomes in the GnomAD database, including 279,892 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 0.45 (18965 hom., cov: 32)
  • Exomes 𝑓: 0.58 (260927 hom.)
• Consequence: SLC28A2 NM_004212.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.6209626E-6).
• BP6: Variant 15-45253280-C-T is Benign according to our data. Variant chr15-45253280-C-T is described in ClinVar as [Benign]. Clinvar id is 1269551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC28A2	NM_004212.4	c.65C>T	p.Pro22Leu	missense_variant	2/18	ENST00000347644.8	NP_004203.2
SLC28A2-AS1	NR_120335.1	n.180+586G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC28A2	ENST00000347644.8	c.65C>T	p.Pro22Leu	missense_variant	2/18	1	NM_004212.4	ENSP00000315006	P1
SLC28A2-AS1	ENST00000663463.1	n.56-10750G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68700 AN: 151942 Hom.: 18972 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.474 AC: 118542 AN: 250026 Hom.: 32517 AF XY: 0.491 AC XY: 66311 AN XY: 135038

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.0793

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.582 AC: 848558 AN: 1458176 Hom.: 260927 Cov.: 33 AF XY: 0.581 AC XY: 421374 AN XY: 725480

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.0627

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.452 AC: 68704 AN: 152060 Hom.: 18965 Cov.: 32 AF XY: 0.445 AC XY: 33086 AN XY: 74322

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.0874

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.463

Alfa AF: 0.567 Hom.: 43884

Bravo AF: 0.421

TwinsUK AF: 0.644 AC: 2387

ALSPAC AF: 0.631 AC: 2433

ESP6500AA AF: 0.191 AC: 840

ESP6500EA AF: 0.628 AC: 5402

ExAC AF: 0.474 AC: 57598

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 30315176) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.71
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.056
Sift	Benign	0.55	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.042
MPC		0.042
ClinPred		0.0066	T
GERP RS		-0.81
Varity_R		0.023
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11854484; hg19: chr15-45545478; COSMIC: COSV61664096; COSMIC: COSV61664096;