8-42417442-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001257180.2(SLC20A2):c.*361A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 165,108 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (708 hom., cov: 32)
  • Exomes 𝑓: 0.043 (26 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29

Genes affected

SLC20A2 (HGNC:10947): (solute carrier family 20 member 2) This gene encodes a member of the inorganic phosphate transporter family. The encoded protein is a type 3 sodium-dependent phosphate symporter that plays an important role in phosphate homeostasis by mediating cellular phosphate uptake. The encoded protein also confers susceptibility to viral infection as a gamma-retroviral receptor. Mutations in this gene may play a role in familial idiopathic basal ganglia calcification. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 8-42417442-T-C is Benign according to our data. Variant chr8-42417442-T-C is described in ClinVar as [Benign]. Clinvar id is 363060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC20A2	NM_001257180.2	c.*361A>G		3_prime_UTR_variant	11/11	ENST00000520262.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC20A2	ENST00000520262.6	c.*361A>G		3_prime_UTR_variant	11/11	2	NM_001257180.2	P1
SLC20A2	ENST00000342228.7	c.*361A>G		3_prime_UTR_variant	11/11	1		P1

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10918 AN: 152108 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0898

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0588

GnomAD4 exome AF: 0.0428 AC: 551 AN: 12882 Hom.: 26 Cov.: 0 AF XY: 0.0452 AC XY: 304 AN XY: 6728

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0277

Gnomad4 ASJ exome AF: 0.00508

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0627

Gnomad4 FIN exome AF: 0.0571

Gnomad4 NFE exome AF: 0.0215

Gnomad4 OTH exome AF: 0.0354

GnomAD4 genome AF: 0.0719 AC: 10947 AN: 152226 Hom.: 708 Cov.: 32 AF XY: 0.0754 AC XY: 5613 AN XY: 74426

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0902

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0296 Hom.: 224

Bravo AF: 0.0704

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic basal ganglia calcification 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	13
Dann	Benign	0.88

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: rs3763510; hg19: chr8-42274960;