rs115989387

Variant names:

• chr8-42417690-T-A
• rs115989387
• NM_001257180.2:c.*113A>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001257180.2(SLC20A2):​c.*113A>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 0.00136 in 1,174,758 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (1 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-42417690-T-A is Benign according to our data. Variant chr8-42417690-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 363065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00555 (844/152044) while in subpopulation AFR AF= 0.0193 (802/41458). AF 95% confidence interval is 0.0182. There are 14 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 844 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC20A2	NM_001257180.2	c.*113A>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000520262.6	NP_001244109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC20A2	ENST00000520262	c.*113A>T		3_prime_UTR_variant	Exon 11 of 11	2	NM_001257180.2	ENSP00000429754.1
SLC20A2	ENST00000342228	c.*113A>T		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000340465.3
SLC20A2	ENST00000520179.5	c.*113A>T		downstream_gene_variant		1		ENSP00000429712.1

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 836 AN: 151926 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000733 AC: 750 AN: 1022714 Hom.: 1 Cov.: 13 AF XY: 0.000633 AC XY: 326 AN XY: 514732

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00301

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000751

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000439

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00555 AC: 844 AN: 152044 Hom.: 14 Cov.: 32 AF XY: 0.00537 AC XY: 399 AN XY: 74328

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00423 Hom.: 1

Bravo AF: 0.00619

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Dec 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Idiopathic basal ganglia calcification 1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.77
CADD	Benign	0.25
DANN	Benign	0.79

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: rs115989387; hg19: chr8-42275208;