chr6-73363244-GCTGA-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001017361.3(KHDC3L):c.322_325del(p.Asp108IlefsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
KHDC3L
NM_001017361.3 frameshift
NM_001017361.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
KHDC3L (HGNC:33699): (KH domain containing 3 like, subcortical maternal complex member) The protein encoded by this gene belongs to the KHDC1 family, members of which contain an atypical KH domain that may not bind RNA like canonical KH domains. This gene is specifically expressed in the oocytes, and recent studies suggest that it may function as a regulator of genomic imprinting in the oocyte. Mutations in this gene are associated with recurrent biparental complete hydatidiform mole. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.511 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-73363244-GCTGA-G is Pathogenic according to our data. Variant chr6-73363244-GCTGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 30927.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KHDC3L | NM_001017361.3 | c.322_325del | p.Asp108IlefsTer30 | frameshift_variant | 2/3 | ENST00000370367.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KHDC3L | ENST00000370367.4 | c.322_325del | p.Asp108IlefsTer30 | frameshift_variant | 2/3 | 1 | NM_001017361.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251390Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461862Hom.: 0 AF XY: 0.0000385 AC XY: 28AN XY: 727234
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74358
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hydatidiform mole, recurrent, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2013 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at