13-93227466-T-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_005708.5(GPC6):c.10T>A(p.Trp4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,613,784 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 3 hom. )
Consequence
GPC6
NM_005708.5 missense
NM_005708.5 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 1.24
Genes affected
GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0056159794).
BP6
?
Variant 13-93227466-T-A is Benign according to our data. Variant chr13-93227466-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 282088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC6 | NM_005708.5 | c.10T>A | p.Trp4Arg | missense_variant | 1/9 | ENST00000377047.9 | |
GPC6 | XM_047429990.1 | c.-51+784T>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC6 | ENST00000377047.9 | c.10T>A | p.Trp4Arg | missense_variant | 1/9 | 1 | NM_005708.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152092Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000537 AC: 135AN: 251278Hom.: 1 AF XY: 0.000545 AC XY: 74AN XY: 135808
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GnomAD4 exome AF: 0.000155 AC: 226AN: 1461574Hom.: 3 Cov.: 31 AF XY: 0.000154 AC XY: 112AN XY: 727078
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GnomAD4 genome ? AF: 0.000243 AC: 37AN: 152210Hom.: 1 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74410
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 19, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Autosomal recessive omodysplasia Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
GPC6-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 04, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0126);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at