chr8-42417423-G-A

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

2

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]

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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 UniProt
SLC20A2NM_001257180.2 linkuse as main transcriptc.*380C>T 3_prime_UTR_variant 11/11 ENST00000520262.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC20A2ENST00000520262.6 linkuse as main transcriptc.*380C>T 3_prime_UTR_variant 11/112 NM_001257180.2 P1
SLC20A2ENST00000342228.7 linkuse as main transcriptc.*380C>T 3_prime_UTR_variant 11/111 P1

Frequencies

GnomAD3 genomes
AF:
0.0151
AC:
2290
AN:
152128
Hom.:
24
Cov.:
32
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.:
1
Cov.:
0
AF XY:
0.0124
AC XY:
46
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.:
24
Cov.:
32
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.:
9
Bravo
AF:
0.0140
Asia WGS
AF:
0.0100
AC:
37
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Idiopathic basal ganglia calcification 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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.

Other links and lift over

dbSNP: rs72643203; hg19: chr8-42274941; API