X-133302977-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001448.3(GPC4):c.1561A>G(p.Lys521Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000314 in 1,209,665 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001448.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPC4 | NM_001448.3 | c.1561A>G | p.Lys521Glu | missense_variant | 9/9 | ENST00000370828.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPC4 | ENST00000370828.4 | c.1561A>G | p.Lys521Glu | missense_variant | 9/9 | 1 | NM_001448.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000179 AC: 2AN: 111561Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 33751
GnomAD3 exomes AF: 0.0000382 AC: 7AN: 183166Hom.: 0 AF XY: 0.0000591 AC XY: 4AN XY: 67696
GnomAD4 exome AF: 0.0000328 AC: 36AN: 1098104Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 8AN XY: 363458
GnomAD4 genome ? AF: 0.0000179 AC: 2AN: 111561Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 33751
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 17, 2023 | The c.1561A>G (p.K521E) alteration is located in exon 9 (coding exon 9) of the GPC4 gene. This alteration results from a A to G substitution at nucleotide position 1561, causing the lysine (K) at amino acid position 521 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at