15-84888799-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004213.5(SLC28A1):c.124T>C(p.Leu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,554,436 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (12 hom., cov: 32)
  • Exomes 𝑓: 0.011 (120 hom.)
• Consequence: SLC28A1 NM_004213.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.988

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 (BayesDel_noAF=-0.91).
• BP6: Variant 15-84888799-T-C is Benign according to our data. Variant chr15-84888799-T-C is described in ClinVar as [Benign]. Clinvar id is 3042333.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0114 (15971/1402188) while in subpopulation EAS AF= 0.0182 (655/35984). AF 95% confidence interval is 0.017. There are 120 homozygotes in gnomad4_exome. There are 7554 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.124T>C	p.Leu42=	synonymous_variant	4/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.124T>C	p.Leu42=	synonymous_variant	4/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.124T>C	p.Leu42=	synonymous_variant	3/18	1		P1
SLC28A1	ENST00000338602.6	c.124T>C	p.Leu42=	synonymous_variant	4/7	1
SLC28A1	ENST00000538177.5	c.124T>C	p.Leu42=	synonymous_variant	3/15	2

Frequencies

GnomAD3 genomes AF: 0.00929 AC: 1413 AN: 152130 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00545

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00909 AC: 1440 AN: 158484 Hom.: 11 AF XY: 0.00830 AC XY: 696 AN XY: 83892

Gnomad AFR exome AF: 0.00646

Gnomad AMR exome AF: 0.00984

Gnomad ASJ exome AF: 0.00983

Gnomad EAS exome AF: 0.00995

Gnomad SAS exome AF: 0.00244

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0123

GnomAD4 exome AF: 0.0114 AC: 15971 AN: 1402188 Hom.: 120 Cov.: 31 AF XY: 0.0109 AC XY: 7554 AN XY: 692014

Gnomad4 AFR exome AF: 0.00545

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.0182

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.00929 AC: 1415 AN: 152248 Hom.: 12 Cov.: 32 AF XY: 0.00844 AC XY: 628 AN XY: 74440

Gnomad4 AFR AF: 0.00549

Gnomad4 AMR AF: 0.0127

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0113 Hom.: 10

Bravo AF: 0.0103

Asia WGS AF: 0.00491 AC: 17 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

Nov 08, 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
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.19
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17222302; hg19: chr15-85432030;