rs6841

Positions:

• chr8-42416746-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257180.2(SLC20A2):​c.*1057C>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 0.192 in 152,552 control chromosomes in the GnomAD database, including 5,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5914 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.434

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=-0.89).
• BP6: Variant 8-42416746-G-C is Benign according to our data. Variant chr8-42416746-G-C is described in ClinVar as [Benign]. Clinvar id is 363053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC20A2	NM_001257180.2	c.*1057C>G		3_prime_UTR_variant	11/11	ENST00000520262.6	NP_001244109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC20A2	ENST00000520262.6	c.*1057C>G		3_prime_UTR_variant	11/11	2	NM_001257180.2	ENSP00000429754	P1
SLC20A2	ENST00000342228.7	c.*1057C>G		3_prime_UTR_variant	11/11	1		ENSP00000340465	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29183 AN: 151984 Hom.: 5881 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0900

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.120 AC: 54 AN: 450 Hom.: 1 Cov.: 0 AF XY: 0.119 AC XY: 32 AN XY: 270

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.192 AC: 29267 AN: 152102 Hom.: 5914 Cov.: 32 AF XY: 0.190 AC XY: 14154 AN XY: 74368

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0904

Gnomad4 SAS AF: 0.0937

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.155

Alfa AF: 0.125 Hom.: 444

Bravo AF: 0.202

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	-0.89
CADD	Benign	0.98
DANN	Benign	0.48

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: rs6841; hg19: chr8-42274264; COSMIC: COSV60604921; COSMIC: COSV60604921;