chr10-101062679-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_030929.5(KAZALD1):c.87C>T(p.Gly29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,544,824 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.014 ( 39 hom., cov: 33)
Exomes 𝑓: 0.0015 ( 52 hom. )
Consequence
KAZALD1
NM_030929.5 synonymous
NM_030929.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.517
Genes affected
KAZALD1 (HGNC:25460): (Kazal type serine peptidase inhibitor domain 1) This gene encodes a secreted member of the insulin growth factor-binding protein (IGFBP) superfamily. The protein contains an insulin growth factor-binding domain in its N-terminal region, a Kazal-type serine protease inhibitor and follistatin-like domain in its central region, and an immunoglobulin-like domain in its C-terminal region. Studies of the mouse ortholog suggest that this protein may function in bone development and bone regeneration. This gene is hypomethylated and over-expressed in high-grade glioma compared to low-grade glioma, and thus the hypomethylated gene may be associated with cell proliferation and the shorter survival of patients with high-grade glioma. It is also one of numerous genes found to be deleted in a novel 5.54 Mb interstitial deletion, which is associated with multiple congenital anomalies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 10-101062679-C-T is Benign according to our data. Variant chr10-101062679-C-T is described in ClinVar as [Benign]. Clinvar id is 781215.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.517 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2105/152358) while in subpopulation AFR AF= 0.0474 (1973/41592). AF 95% confidence interval is 0.0457. There are 39 homozygotes in gnomad4. There are 988 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 39 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAZALD1 | NM_030929.5 | c.87C>T | p.Gly29= | synonymous_variant | 2/5 | ENST00000370200.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAZALD1 | ENST00000370200.6 | c.87C>T | p.Gly29= | synonymous_variant | 2/5 | 1 | NM_030929.5 | P1 | |
KAZALD1 | ENST00000470106.1 | n.44-307C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
KAZALD1 | ENST00000477979.5 | n.112+564C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0138 AC: 2098AN: 152240Hom.: 39 Cov.: 33
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GnomAD3 exomes AF: 0.00337 AC: 484AN: 143712Hom.: 13 AF XY: 0.00227 AC XY: 181AN XY: 79814
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GnomAD4 exome AF: 0.00152 AC: 2112AN: 1392466Hom.: 52 Cov.: 32 AF XY: 0.00134 AC XY: 921AN XY: 689014
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GnomAD4 genome ? AF: 0.0138 AC: 2105AN: 152358Hom.: 39 Cov.: 33 AF XY: 0.0133 AC XY: 988AN XY: 74502
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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 submitter | clinical testing | Invitae | Jul 16, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at