8-42417828-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001257180.2(SLC20A2):​c.1934T>A​(p.Met645Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,614,116 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 3 hom. )

Consequence

SLC20A2
NM_001257180.2 missense

Scores

1
2
16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.32
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 -13 ACMG points.

PP2
Missense variant in the SLC20A2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 11 curated benign missense variants. Gene score misZ: 2.6315 (below the threshold of 3.09). Trascript score misZ: 3.281 (above the threshold of 3.09). GenCC associations: The gene is linked to basal ganglia calcification, idiopathic, 1, bilateral striopallidodentate calcinosis.
BP4
Computational evidence support a benign effect (MetaRNN=0.010433137).
BP6
Variant 8-42417828-A-T is Benign according to our data. Variant chr8-42417828-A-T is described in ClinVar as [Benign]. Clinvar id is 708041.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000184 (28/152262) while in subpopulation EAS AF= 0.00542 (28/5170). AF 95% confidence interval is 0.00385. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC20A2NM_001257180.2 linkc.1934T>A p.Met645Lys missense_variant Exon 11 of 11 ENST00000520262.6 NP_001244109.1 Q08357A0A384MR38

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC20A2ENST00000520262.6 linkc.1934T>A p.Met645Lys missense_variant Exon 11 of 11 2 NM_001257180.2 ENSP00000429754.1 Q08357
SLC20A2ENST00000342228.7 linkc.1934T>A p.Met645Lys missense_variant Exon 11 of 11 1 ENSP00000340465.3 Q08357
SLC20A2ENST00000520179.5 linkc.1934T>A p.Met645Lys missense_variant Exon 11 of 11 1 ENSP00000429712.1 Q08357

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00540
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000478
AC:
120
AN:
251282
Hom.:
3
AF XY:
0.000434
AC XY:
59
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00642
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000144
AC:
210
AN:
1461854
Hom.:
3
Cov.:
30
AF XY:
0.000150
AC XY:
109
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00499
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152262
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00542
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000326
Hom.:
0
Bravo
AF:
0.000272
ExAC
AF:
0.000445
AC:
54
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
20
DANN
Benign
0.84
DEOGEN2
Benign
0.070
T;T;T
Eigen
Benign
-0.16
Eigen_PC
Benign
0.088
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.71
.;.;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.010
T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
0.33
N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.65
N;N;N
REVEL
Uncertain
0.41
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.55
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.52
MVP
0.70
MPC
0.98
ClinPred
0.093
T
GERP RS
6.2
Varity_R
0.24
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: rs115580154; hg19: chr8-42275346; API