rs779594202

chr17-46171644-T-Achr17-46171644-T-Cchr17-46171644-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015443.4(KANSL1):c.500A>T(p.His167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H167R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: KANSL1 NM_015443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1074757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.500A>T	p.His167Leu	missense_variant	2/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.500A>T	p.His167Leu	missense_variant	2/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	22
Dann	Benign	0.95
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.096
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.67	D;D;N;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N;.;.;.;.;N;.;.;.
REVEL	Benign	0.16
Sift	Benign	0.67	T;.;.;.;.;T;.;.;.
Sift4G	Benign	0.78	T;T;T;.;T;T;.;.;.
Vest4		0.62
MutPred		0.15		Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);Loss of catalytic residue at H167 (P = 0.0636);
MVP		0.54
MPC		0.019
ClinPred		0.22	T
GERP RS		5.0
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-44249010;