rs45584739

Positions:

• chr15-84943499-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004213.5(SLC28A1):​c.1636T>C​(p.Ser546Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000617 in 1,613,988 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (6 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 6.12

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018100917).
• BP6: Variant 15-84943499-T-C is Benign according to our data. Variant chr15-84943499-T-C is described in ClinVar as [Benign]. Clinvar id is 634887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.1636T>C	p.Ser546Pro	missense_variant	16/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.1636T>C	p.Ser546Pro	missense_variant	16/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.1636T>C	p.Ser546Pro	missense_variant	15/18	1		P1
SLC28A1	ENST00000538177.5	c.1138T>C	p.Ser380Pro	missense_variant	12/15	2

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 526 AN: 152174 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000863 AC: 217 AN: 251480 Hom.: 5 AF XY: 0.000486 AC XY: 66 AN XY: 135916

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000322 AC: 470 AN: 1461696 Hom.: 6 Cov.: 30 AF XY: 0.000263 AC XY: 191 AN XY: 727158

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000729

GnomAD4 genome AF: 0.00345 AC: 526 AN: 152292 Hom.: 6 Cov.: 33 AF XY: 0.00328 AC XY: 244 AN XY: 74464

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000677 Hom.: 1

Bravo AF: 0.00361

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00105 AC: 128

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SLC28A1: BS1, BS2 -

SLC28A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 24, 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). -

Uridine-cytidineuria Other:1

Affects, no assertion criteria provided

literature only

OMIM

Jun 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.97	D;D;.
MetaRNN	Benign	0.018	T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.13	T;D;D
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.88	P;D;D
Vest4		0.97
MVP		0.50
MPC		0.49
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.97
gMVP		0.97

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: rs45584739; hg19: chr15-85486730;