8-42417423-G-A

Variant summary

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

The NM_001257180.2(SLC20A2):c.*380C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 159,292 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.474

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 8-42417423-G-A is Benign according to our data. Variant chr8-42417423-G-A is described in ClinVar as [Benign]. Clinvar id is 363059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2289/152246) while in subpopulation NFE AF= 0.0229 (1558/68004). AF 95% confidence interval is 0.022. There are 24 homozygotes in gnomad4. There are 1055 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC20A2	NM_001257180.2	c.*380C>T		3_prime_UTR_variant	11/11	ENST00000520262.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC20A2	ENST00000520262.6	c.*380C>T		3_prime_UTR_variant	11/11	2	NM_001257180.2	P1
SLC20A2	ENST00000342228.7	c.*380C>T		3_prime_UTR_variant	11/11	1		P1

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2290 AN: 152128 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00389

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0229

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0142 AC: 100 AN: 7046 Hom.: 1 Cov.: 0 AF XY: 0.0124 AC XY: 46 AN XY: 3722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00778

Gnomad4 ASJ exome AF: 0.0510

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00417

Gnomad4 FIN exome AF: 0.0270

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0150 AC: 2289 AN: 152246 Hom.: 24 Cov.: 32 AF XY: 0.0142 AC XY: 1055 AN XY: 74432

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0229

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0198 Hom.: 9

Bravo AF: 0.0140

Asia WGS AF: 0.0100 AC: 37 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	-0.54
Cadd	Benign	8.2
Dann	Benign	0.56

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: rs72643203; hg19: chr8-42274941;