Genetic Variant ENST00000572218.5:n.8638dupT (chr17-46030372-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000572218.5(KANSL1):n.8638dupT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 148,080 control chromosomes in the GnomAD database, including 47 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 47 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KANSL1
ENST00000572218.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Publications

0 publications found

Variant links:

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]

KANSL1 Gene-Disease associations (from GenCC):

Koolen-de Vries syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
Koolen-de Vries syndrome due to a point mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KANSL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0214 (3174/148080) while in subpopulation NFE AF = 0.0306 (2047/66926). AF 95% confidence interval is 0.0295. There are 47 homozygotes in GnomAd4. There are 1606 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 3174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.*1103dupT		3_prime_UTR_variant	Exon 15 of 15	ENST00000432791.7	NP_056258.1	Q7Z3B3-1A0A024R9Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 link	c.*1103dupT		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3176

AN:

147980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00423

Gnomad AMI

AF:

0.0993

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00879

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0188

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0214

AC:

3174

AN:

148080

Hom.:

Cov.:

AF XY:

0.0223

AC XY:

1606

AN XY:

72064

show subpopulations

African (AFR)

AF:

0.00419

AC:

169

AN:

40328

American (AMR)

AF:

0.0171

AC:

255

AN:

14906

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

AN:

3426

East Asian (EAS)

AF:

0.000198

AC:

AN:

5054

South Asian (SAS)

AF:

0.00882

AC:

AN:

4648

European-Finnish (FIN)

AF:

0.0457

AC:

437

AN:

9556

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0306

AC:

2047

AN:

66926

Other (OTH)

AF:

0.0186

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

146

291

437

582

728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0181

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic intellectual disability

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism

(source)

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

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ENST00000572218.5:n.8638dupT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over