rs142062936
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_015443.4(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
NM_015443.4 missense
NM_015443.4 missense
Scores
8
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 | UniProt |
---|---|---|---|---|---|---|---|
KANSL1 | NM_015443.4 | c.1285C>A | p.Pro429Thr | missense_variant | 2/15 | ENST00000432791.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KANSL1 | ENST00000432791.7 | c.1285C>A | p.Pro429Thr | missense_variant | 2/15 | 1 | NM_015443.4 | 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 | Invitae | 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
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