Variant 8-42417423-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.474

Variant links:

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]

SLC20A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 2289 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC20A2	NM_001257180.2 linkuse as main transcript	c.*380C>T		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 linkuse as main transcript	c.*380C>T		3_prime_UTR_variant	11/11	2	NM_001257180.2	ENSP00000429754	P1
SLC20A2	ENST00000342228.7 linkuse as main transcript	c.*380C>T		3_prime_UTR_variant	11/11	1		ENSP00000340465	P1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2290

AN:

152128

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0124

AC XY:

AN XY:

3722

show subpopulations

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.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74432

show subpopulations

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.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over