Genetic Variant KANSL3:p.Ala642Thr (chr2-96605329-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001115016.3(KANSL3):c.1924G>A(p.Ala642Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KANSL3
NM_001115016.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

Publications

0 publications found

Variant links:

Genes affected

KANSL3 (HGNC:25473): (KAT8 regulatory NSL complex subunit 3) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046292573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115016.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KANSL3	NM_001115016.3	MANE Select	c.1924G>A	p.Ala642Thr	missense	Exon 15 of 21	NP_001108488.1	Q9P2N6-3
KANSL3	NM_001349256.2		c.2002G>A	p.Ala668Thr	missense	Exon 16 of 22	NP_001336185.1
KANSL3	NM_001349257.2		c.2002G>A	p.Ala668Thr	missense	Exon 16 of 22	NP_001336186.1	Q9P2N6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KANSL3	ENST00000431828.6	TSL:1 MANE Select	c.1924G>A	p.Ala642Thr	missense	Exon 15 of 21	ENSP00000396749.1	Q9P2N6-3
KANSL3	ENST00000354204.10	TSL:1	n.*1766G>A		non_coding_transcript_exon	Exon 15 of 21	ENSP00000346144.7	F8WEN2
KANSL3	ENST00000420155.5	TSL:1	n.2002G>A		non_coding_transcript_exon	Exon 16 of 21	ENSP00000414426.1	Q9P2N6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724066

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25986

East Asian (EAS)

AF:

0.00

AC:

AN:

39594

South Asian (SAS)

AF:

0.00

AC:

AN:

86030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109000

Other (OTH)

AF:

0.0000166

AC:

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.77

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.71

M_CAP

Benign

0.0045

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

PhyloP100

0.010

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.40

REVEL

Benign

0.040

Sift

Benign

0.43

Sift4G

Benign

0.39

Polyphen

0.0010

Vest4

0.10

MVP

0.11

MPC

0.20

ClinPred

0.045

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.11

Mutation Taster

=97/3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over