rs8187758

chr15-84905644-C-A

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.709C>A(p.Gln237Lys) variant causes a missense change. The variant allele was found at a frequency of 0.25 in 1,608,760 control chromosomes in the GnomAD database, including 53,745 homozygotes. In-silico tool predicts 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 0.23 (4358 hom., cov: 33)
  • Exomes 𝑓: 0.25 (49387 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.80

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=0.005893916).
• BP6: Variant 15-84905644-C-A is Benign according to our data. Variant chr15-84905644-C-A is described in ClinVar as [Benign]. Clinvar id is 3059004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.709C>A	p.Gln237Lys	missense_variant	8/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.709C>A	p.Gln237Lys	missense_variant	8/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.709C>A	p.Gln237Lys	missense_variant	7/18	1		P1
SLC28A1	ENST00000538177.5	c.709C>A	p.Gln237Lys	missense_variant	7/15	2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34972 AN: 151980 Hom.: 4345 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.281 AC: 70544 AN: 251152 Hom.: 11327 AF XY: 0.281 AC XY: 38166 AN XY: 135738

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.429

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.252 AC: 366592 AN: 1456662 Hom.: 49387 Cov.: 31 AF XY: 0.256 AC XY: 185300 AN XY: 724882

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.230 AC: 35018 AN: 152098 Hom.: 4358 Cov.: 33 AF XY: 0.235 AC XY: 17455 AN XY: 74354

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.214

Alfa AF: 0.228 Hom.: 8209

Bravo AF: 0.232

TwinsUK AF: 0.238 AC: 881

ALSPAC AF: 0.249 AC: 960

ESP6500AA AF: 0.171 AC: 752

ESP6500EA AF: 0.224 AC: 1926

ExAC AF: 0.273 AC: 33199

Asia WGS AF: 0.362 AC: 1259 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.225

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

Nov 01, 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	0.14
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	24
Dann	Benign	0.96
DEOGEN2	Benign	0.021	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;D;.
MetaRNN	Benign	0.0059	T;T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	0.0000051	P;P;P;P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		1.0	D;P;P
Vest4		0.40
MPC		0.49
ClinPred		0.035	T
GERP RS		4.0
Varity_R		0.73
gMVP		0.78

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: rs8187758; hg19: chr15-85448875; COSMIC: COSV54476274;