X-133536129-GCA-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_004484.4(GPC3):​c.1736_1737delTG​(p.Val579fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Consequence

GPC3
NM_004484.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43
Variant links:
Genes affected
GPC3 (HGNC:4451): (glypican 3) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00402 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPC3NM_004484.4 linkuse as main transcriptc.1736_1737delTG p.Val579fs frameshift_variant 8/8 ENST00000370818.8 NP_004475.1 P51654-1Q53H15I6QTG3
GPC3NM_001164617.2 linkuse as main transcriptc.1805_1806delTG p.Val602fs frameshift_variant 9/9 NP_001158089.1 P51654-3Q53H15
GPC3NM_001164618.2 linkuse as main transcriptc.1688_1689delTG p.Val563fs frameshift_variant 8/8 NP_001158090.1 Q53H15B4DTD8
GPC3NM_001164619.2 linkuse as main transcriptc.1574_1575delTG p.Val525fs frameshift_variant 7/7 NP_001158091.1 P51654-2Q53H15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPC3ENST00000370818.8 linkuse as main transcriptc.1736_1737delTG p.Val579fs frameshift_variant 8/81 NM_004484.4 ENSP00000359854.3 P51654-1

Frequencies

GnomAD3 genomes
Cov.:
21
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
21

ClinVar

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

Submissions by phenotype

Simpson-Golabi-Behmel syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMGZ Medical Genetics CenterMar 24, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-132670157; API