rs770738115

Positions:

• chr17-46172032-C-G
• chr17-46172032-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015443.4(KANSL1):​c.112G>C​(p.Gly38Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: KANSL1 NM_015443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38259047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.112G>C	p.Gly38Arg	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.112G>C	p.Gly38Arg	missense_variant	2/15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	.;.;.;.;.;.;.;.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;.;.;.;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.4	N;.;.;.;.;N;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;.;.;.;.;D;.;.;.
Sift4G	Uncertain	0.012	D;D;D;.;D;D;.;.;.
Vest4		0.88
MutPred		0.15		Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP		0.52
MPC		0.15
ClinPred		0.85	D
GERP RS		6.0
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs770738115; hg19: chr17-44249398;