8-41932248-C-G

Variant names:

• chr8-41932248-C-G
• NM_006766.5:c.5972G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006766.5(KAT6A):​c.5972G>C​(p.Gly1991Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1991V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KAT6A NM_006766.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

Genes affected

KAT6A (HGNC:13013): (lysine acetyltransferase 6A) This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases. The protein is composed of a nuclear localization domain, a double C2H2 zinc finger domain that binds to acetylated histone tails, a histone acetyl-transferase domain, a glutamate/aspartate-rich region, and a serine- and methionine-rich transactivation domain. It is part of a complex that acetylates lysine-9 residues in histone 3, and in addition, it acts as a co-activator for several transcription factors. Allelic variants of this gene are associated with an autosomal dominant form of cognitive disability. Chromosomal translocations of this gene are associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6A	NM_006766.5	c.5972G>C	p.Gly1991Ala	missense_variant	Exon 17 of 17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8	c.5972G>C	p.Gly1991Ala	missense_variant	Exon 17 of 17	1	NM_006766.5	ENSP00000265713.2
KAT6A	ENST00000406337.6	c.5978G>C	p.Gly1993Ala	missense_variant	Exon 18 of 18	5		ENSP00000385888.2
KAT6A	ENST00000396930.4	c.5972G>C	p.Gly1991Ala	missense_variant	Exon 18 of 18	5		ENSP00000380136.3
KAT6A	ENST00000649817.1	c.4652G>C	p.Gly1551Ala	missense_variant	Exon 11 of 11			ENSP00000497780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460892 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	.;D;D
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;.;T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.81	.;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-4.2	.;D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	.;D;D
Sift4G	Uncertain	0.058	.;T;T
Polyphen		0.90	.;P;P
Vest4		0.79, 0.67
MutPred		0.26		.;Gain of glycosylation at S1996 (P = 0.107);Gain of glycosylation at S1996 (P = 0.107);
MVP		0.71
MPC		0.20
ClinPred		0.93	D
GERP RS		5.9
Varity_R		0.63
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-41789766;