Genetic Variant NM_182710.3:c.615+28T>C (chr11-65713695-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182710.3(KAT5):c.615+28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 1,613,820 control chromosomes in the GnomAD database, including 648,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 56950 hom., cov: 31)

Exomes 𝑓: 0.90 ( 591253 hom. )

Consequence

KAT5
NM_182710.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.322

Publications

21 publications found

Variant links:

Genes affected

KAT5 (HGNC:5275): (lysine acetyltransferase 5) The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

KAT5 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

KAT5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182710.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KAT5	NM_182710.3	MANE Select	c.615+28T>C	intron	N/A	NP_874369.1	Q92993-3
KAT5	NM_006388.4		c.516+28T>C	intron	N/A	NP_006379.2
KAT5	NM_001206833.2		c.459+28T>C	intron	N/A	NP_001193762.1	Q92993-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KAT5	ENST00000341318.9	TSL:1 MANE Select	c.615+28T>C	intron	N/A	ENSP00000340330.4	Q92993-3
KAT5	ENST00000377046.7	TSL:1	c.516+28T>C	intron	N/A	ENSP00000366245.3	Q92993-1
KAT5	ENST00000530446.5	TSL:1	c.459+28T>C	intron	N/A	ENSP00000434765.1	Q92993-4

Frequencies

GnomAD3 genomes

AF:

0.863

AC:

131186

AN:

152094

Hom.:

56911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.771

Gnomad AMI

AF:

0.846

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.895

Gnomad EAS

AF:

0.893

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.902

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.871

GnomAD2 exomes

AF:

0.870

AC:

218784

AN:

251376

AF XY:

0.867

show subpopulations

Gnomad AFR exome

AF:

0.765

Gnomad AMR exome

AF:

0.864

Gnomad ASJ exome

AF:

0.885

Gnomad EAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.903

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.894

GnomAD4 exome

AF:

0.898

AC:

1312306

AN:

1461608

Hom.:

591253

Cov.:

AF XY:

0.894

AC XY:

649874

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.766

AC:

25643

AN:

33478

American (AMR)

AF:

0.866

AC:

38722

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

23103

AN:

26130

East Asian (EAS)

AF:

0.894

AC:

35476

AN:

39700

South Asian (SAS)

AF:

0.728

AC:

62794

AN:

86246

European-Finnish (FIN)

AF:

0.903

AC:

48259

AN:

53416

Middle Eastern (MID)

AF:

0.891

AC:

5142

AN:

5768

European-Non Finnish (NFE)

AF:

0.917

AC:

1019432

AN:

1111764

Other (OTH)

AF:

0.890

AC:

53735

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7801

15602

23402

31203

39004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21456

42912

64368

85824

107280

<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

AF:

0.863

AC:

131286

AN:

152212

Hom.:

56950

Cov.:

AF XY:

0.861

AC XY:

64060

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.772

AC:

32026

AN:

41510

American (AMR)

AF:

0.871

AC:

13321

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

3109

AN:

3472

East Asian (EAS)

AF:

0.894

AC:

4620

AN:

5170

South Asian (SAS)

AF:

0.721

AC:

3477

AN:

4824

European-Finnish (FIN)

AF:

0.902

AC:

9574

AN:

10612

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.916

AC:

62299

AN:

68012

Other (OTH)

AF:

0.869

AC:

1834

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

895

1789

2684

3578

4473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.897

Hom.:

114451

Bravo

AF:

0.859

Asia WGS

AF:

0.793

AC:

2759

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.4

(source)

DANN

Benign

0.27

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over