rs142062936
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The ENST00000432791.7(KANSL1):c.1285C>A(p.Pro429Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000805 in 1,602,262 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00043 ( 1 hom., cov: 35)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
KANSL1
ENST00000432791.7 missense
ENST00000432791.7 missense
Scores
9
8
Clinical Significance
Conservation
PhyloP100: 4.77
Genes affected
KANSL1 (HGNC:24565): (KAT8 regulatory NSL complex subunit 1) This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06887427).
BP6
Variant 17-46170859-G-T is Benign according to our data. Variant chr17-46170859-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 205787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000427 (65/152296) while in subpopulation AFR AF= 0.00149 (62/41546). AF 95% confidence interval is 0.00119. There are 1 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
High AC in GnomAd4 at 65 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.1285C>A | p.Pro429Thr | missense_variant | 2/15 | ENST00000432791.7 | NP_056258.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KANSL1 | ENST00000432791.7 | c.1285C>A | p.Pro429Thr | missense_variant | 2/15 | 1 | NM_015443.4 | ENSP00000387393 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000427 AC: 65AN: 152178Hom.: 1 Cov.: 35
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GnomAD3 exomes AF: 0.0000697 AC: 17AN: 243898Hom.: 0 AF XY: 0.0000607 AC XY: 8AN XY: 131836
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GnomAD4 exome AF: 0.0000441 AC: 64AN: 1449966Hom.: 0 Cov.: 30 AF XY: 0.0000403 AC XY: 29AN XY: 720150
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GnomAD4 genome AF: 0.000427 AC: 65AN: 152296Hom.: 1 Cov.: 35 AF XY: 0.000457 AC XY: 34AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2020 | - - |
Koolen-de Vries syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 26, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;D;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;.;D;.;.;.
Sift4G
Uncertain
D;D;D;.;D;D;.;.;.
Vest4
MVP
MPC
0.060
ClinPred
T
GERP RS
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