17-46031116-A-AGCCCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015443.4(KANSL1):c.*359_*360insAGAGGGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 273,302 control chromosomes in the GnomAD database, including 3,792 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2096 hom., cov: 28)
  • Exomes 𝑓: 0.14 (1696 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.11

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 -10 ACMG points.

• BP6: Variant 17-46031116-A-AGCCCTCT is Benign according to our data. Variant chr17-46031116-A-AGCCCTCT is described in ClinVar as [Benign]. Clinvar id is 323758.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.*359_*360insAGAGGGC		3_prime_UTR_variant	15/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.*359_*360insAGAGGGC		3_prime_UTR_variant	15/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21717 AN: 151880 Hom.: 2098 Cov.: 28

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.140 AC: 17029 AN: 121304 Hom.: 1696 Cov.: 0 AF XY: 0.138 AC XY: 8736 AN XY: 63218

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.000219

Gnomad4 SAS exome AF: 0.0567

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.143 AC: 21706 AN: 151998 Hom.: 2096 Cov.: 28 AF XY: 0.134 AC XY: 9933 AN XY: 74314

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.180

Alfa AF: 0.157 Hom.: 224

Bravo AF: 0.147

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113448888; hg19: chr17-44108482;