chr17-46030121-G-GT

Position:

• chr17-46030121-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_015443.4(KANSL1):​c.*1354dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 144,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.422

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00104 (151/144700) while in subpopulation EAS AF= 0.00163 (8/4914). AF 95% confidence interval is 0.00102. There are 0 homozygotes in gnomad4. There are 80 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.*1354dupA		3_prime_UTR_variant	15/15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791	c.*1354dupA		3_prime_UTR_variant	15/15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 151 AN: 144630 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000999

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000547

Gnomad ASJ AF: 0.00148

Gnomad EAS AF: 0.00162

Gnomad SAS AF: 0.000450

Gnomad FIN AF: 0.000671

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00124

Gnomad OTH AF: 0.000497

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 398 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00104 AC: 151 AN: 144700 Hom.: 0 Cov.: 27 AF XY: 0.00114 AC XY: 80 AN XY: 70268

Gnomad4 AFR AF: 0.000996

Gnomad4 AMR AF: 0.000547

Gnomad4 ASJ AF: 0.00148

Gnomad4 EAS AF: 0.00163

Gnomad4 SAS AF: 0.000451

Gnomad4 FIN AF: 0.000671

Gnomad4 NFE AF: 0.00124

Gnomad4 OTH AF: 0.000493

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs67641084; hg19: chr17-44107487;