rs17222295

Variant names:

• chr15-84888803-G-A
• rs17222295
• NM_004213.5:c.128G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_004213.5(SLC28A1):​c.128G>A​(p.Ser43Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000947 in 1,554,684 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0051 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (2 hom.)
• Consequence: SLC28A1 NM_004213.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.677
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026927292).
• BP6: Variant 15-84888803-G-A is Benign according to our data. Variant chr15-84888803-G-A is described in ClinVar as Benign. ClinVar VariationId is 3043971.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00506 (770/152274) while in subpopulation AFR AF = 0.0177 (735/41552). AF 95% confidence interval is 0.0166. There are 7 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	NM_004213.5	MANE Select	c.128G>A	p.Ser43Asn	missense	Exon 4 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.128G>A	p.Ser43Asn	missense	Exon 3 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.128G>A	p.Ser43Asn	missense	Exon 4 of 19	NP_001308651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.128G>A	p.Ser43Asn	missense	Exon 4 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.128G>A	p.Ser43Asn	missense	Exon 3 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000338602.6	TSL:1	c.128G>A	p.Ser43Asn	missense	Exon 4 of 7	ENSP00000341629.2	O00337-2

Frequencies

GnomAD3 genomes AF: 0.00502 AC: 764 AN: 152156 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.000118

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00122 AC: 194 AN: 158522 AF XY: 0.000750

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000794

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000981

Gnomad OTH exome AF: 0.000895

GnomAD4 exome AF: 0.000501 AC: 702 AN: 1402410 Hom.: 2 Cov.: 31 AF XY: 0.000452 AC XY: 313 AN XY: 692128

African (AFR) AF: 0.0170 AC: 539 AN: 31742

American (AMR) AF: 0.00105 AC: 38 AN: 36144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25204

East Asian (EAS) AF: 0.00 AC: 0 AN: 35990

South Asian (SAS) AF: 0.00 AC: 0 AN: 79378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49386

Middle Eastern (MID) AF: 0.00124 AC: 7 AN: 5632

European-Non Finnish (NFE) AF: 0.0000638 AC: 69 AN: 1080794

Other (OTH) AF: 0.000843 AC: 49 AN: 58140

GnomAD4 genome AF: 0.00506 AC: 770 AN: 152274 Hom.: 7 Cov.: 32 AF XY: 0.00482 AC XY: 359 AN XY: 74458

African (AFR) AF: 0.0177 AC: 735 AN: 41552

American (AMR) AF: 0.00111 AC: 17 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00210 Hom.: 5

Bravo AF: 0.00610

ESP6500AA AF: 0.0171 AC: 74

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.000974 AC: 107

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC28A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.5
DANN	Benign	0.65
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.68
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.038
Sift	Benign	0.25	T
Sift4G	Benign	0.17	T
Polyphen		0.063	B
Vest4		0.10
MVP		0.21
MPC		0.073
ClinPred		0.0044	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.18
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17222295; hg19: chr15-85432034;