X-45076726-G-A

Variant names:

• chrX-45076726-G-A
• rs201673109
• NM_001291415.2:c.2888G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001291415.2(KDM6A):​c.2888G>A​(p.Ser963Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 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. S963T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: KDM6A NM_001291415.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39
• Publications: 0 publications found

Genes affected

KDM6A (HGNC:12637): (lysine demethylase 6A) This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

KDM6A Gene-Disease associations (from GenCC):

• Kabuki syndrome 2

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Kabuki syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37930918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291415.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	NM_001291415.2	MANE Select	c.2888G>A	p.Ser963Asn	missense	Exon 19 of 30	NP_001278344.1	A0A087X0R0
	KDM6A	NM_001419809.1		c.2888G>A	p.Ser963Asn	missense	Exon 19 of 31	NP_001406738.1
	KDM6A	NM_001419810.1		c.2786G>A	p.Ser929Asn	missense	Exon 18 of 30	NP_001406739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	ENST00000611820.5	TSL:1 MANE Select	c.2888G>A	p.Ser963Asn	missense	Exon 19 of 30	ENSP00000483595.2	A0A087X0R0
	KDM6A	ENST00000382899.9	TSL:1	c.2753G>A	p.Ser918Asn	missense	Exon 18 of 29	ENSP00000372355.6	F8W8R6
	KDM6A	ENST00000377967.9	TSL:1	c.2732G>A	p.Ser911Asn	missense	Exon 18 of 29	ENSP00000367203.4	O15550

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1059816 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 333486

African (AFR) AF: 0.00 AC: 0 AN: 25554

American (AMR) AF: 0.00 AC: 0 AN: 34811

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18910

East Asian (EAS) AF: 0.00 AC: 0 AN: 29621

South Asian (SAS) AF: 0.00 AC: 0 AN: 52903

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40145

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3991

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 809290

Other (OTH) AF: 0.00 AC: 0 AN: 44591

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.078	T
MutationAssessor	Benign	0.83	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.31
Sift	Benign	0.28	T
Sift4G	Benign	0.47	T
Polyphen		0.020	B
Vest4		0.29
MVP		0.67
MPC		0.10
ClinPred		0.84	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.29
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs201673109; hg19: chrX-44935971;