rs2242046

chr15-84935498-G-Achr15-84935498-G-T

Variant summary

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

The NM_004213.5(SLC28A1):c.1561G>A(p.Asp521Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,130 control chromosomes in the GnomAD database, including 169,648 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 0.35 (11846 hom., cov: 33)
  • Exomes 𝑓: 0.45 (157802 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5131863E-5).
• BP6: Variant 15-84935498-G-A is Benign according to our data. Variant chr15-84935498-G-A is described in ClinVar as [Benign]. Clinvar id is 3059229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.1561G>A	p.Asp521Asn	missense_variant	15/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.1561G>A	p.Asp521Asn	missense_variant	15/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.1561G>A	p.Asp521Asn	missense_variant	14/18	1		P1
SLC28A1	ENST00000538177.5	c.1084-7947G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52685 AN: 152016 Hom.: 11854 Cov.: 33

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.0775

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.388

GnomAD3 exomes AF: 0.374 AC: 93823 AN: 250790 Hom.: 21090 AF XY: 0.387 AC XY: 52540 AN XY: 135618

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.0750

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.435

GnomAD4 exome AF: 0.450 AC: 657428 AN: 1460996 Hom.: 157802 Cov.: 43 AF XY: 0.449 AC XY: 326253 AN XY: 726818

Gnomad4 AFR exome AF: 0.0854

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.0673

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.346 AC: 52660 AN: 152134 Hom.: 11846 Cov.: 33 AF XY: 0.340 AC XY: 25324 AN XY: 74376

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.383

Alfa AF: 0.478 Hom.: 44676

Bravo AF: 0.323

TwinsUK AF: 0.489 AC: 1814

ALSPAC AF: 0.479 AC: 1846

ESP6500AA AF: 0.103 AC: 456

ESP6500EA AF: 0.498 AC: 4278

ExAC AF: 0.375 AC: 45541

Asia WGS AF: 0.147 AC: 513 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC28A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.0
Dann	Benign	0.96
DEOGEN2	Benign	0.0069	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.18	T;.
MetaRNN	Benign	0.000035	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.45	N;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.0080
Sift	Benign	0.13	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.025	B;B
Vest4		0.030
MPC		0.075
ClinPred		0.017	T
GERP RS		-0.14
Varity_R		0.041
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2242046; hg19: chr15-85478729; COSMIC: COSV54478445; COSMIC: COSV54478445;