8-42417540-T-G

Position:

• chr8-42417540-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001257180.2(SLC20A2):​c.*263A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 268,956 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (3 hom.)
• Consequence: SLC20A2 NM_001257180.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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 8-42417540-T-G is Benign according to our data. Variant chr8-42417540-T-G is described in ClinVar as [Benign]. Clinvar id is 363062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00408 (618/151488) while in subpopulation SAS AF= 0.0083 (40/4820). AF 95% confidence interval is 0.00626. There are 6 homozygotes in gnomad4. There are 282 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 618 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC20A2	NM_001257180.2	c.*263A>C		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.*263A>C		3_prime_UTR_variant	11/11	2	NM_001257180.2	ENSP00000429754	P1
SLC20A2	ENST00000342228.7	c.*263A>C		3_prime_UTR_variant	11/11	1		ENSP00000340465	P1

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 617 AN: 151370 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00675

Gnomad OTH AF: 0.00385

GnomAD4 exome AF: 0.00546 AC: 641 AN: 117468 Hom.: 3 Cov.: 0 AF XY: 0.00582 AC XY: 350 AN XY: 60184

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.00355

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.00383

Gnomad4 NFE exome AF: 0.00708

Gnomad4 OTH exome AF: 0.00300

GnomAD4 genome AF: 0.00408 AC: 618 AN: 151488 Hom.: 6 Cov.: 32 AF XY: 0.00381 AC XY: 282 AN XY: 74072

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00675

Gnomad4 OTH AF: 0.00381

Alfa AF: 0.00631 Hom.: 2

Bravo AF: 0.00367

Asia WGS AF: 0.00144 AC: 5 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 12, 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	5.3
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: rs145543019; hg19: chr8-42275058;