rs36076725

chr17-46033166-G-Achr17-46033166-G-Cchr17-46033166-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015443.4(KANSL1):c.2751C>T(p.Phe917=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,600,854 control chromosomes in the GnomAD database, including 32,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2102 hom., cov: 32)
  • Exomes 𝑓: 0.19 (30369 hom.)
• Consequence: KANSL1 NM_015443.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0610

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-46033166-G-A is Benign according to our data. Variant chr17-46033166-G-A is described in ClinVar as [Benign]. Clinvar id is 323765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46033166-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.061 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.2751C>T	p.Phe917=	synonymous_variant	13/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.2751C>T	p.Phe917=	synonymous_variant	13/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21742 AN: 152008 Hom.: 2103 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.143 AC: 33062 AN: 231482 Hom.: 3076 AF XY: 0.146 AC XY: 18214 AN XY: 124628

Gnomad AFR exome AF: 0.0384

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.000623

Gnomad SAS exome AF: 0.0746

Gnomad FIN exome AF: 0.0664

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.193 AC: 279548 AN: 1448726 Hom.: 30369 Cov.: 32 AF XY: 0.190 AC XY: 137063 AN XY: 719498

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.000889

Gnomad4 SAS exome AF: 0.0789

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.143 AC: 21733 AN: 152128 Hom.: 2102 Cov.: 32 AF XY: 0.134 AC XY: 9950 AN XY: 74390

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.178

Alfa AF: 0.195 Hom.: 2515

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Syndromic intellectual disability Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

MAPT-Related Spectrum Disorders Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Koolen-de Vries syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	1.1
Dann	Benign	0.87

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: rs36076725; hg19: chr17-44110532;