rs201673109

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-45076726-G-A
• chrX-45076726-G-C

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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.2888G>A	p.Ser963Asn	missense_variant	Exon 19 of 30	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5	c.2888G>A	p.Ser963Asn	missense_variant	Exon 19 of 30	1	NM_001291415.2	ENSP00000483595.2

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 v4.3

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;.;T;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.38	T;T;T;T;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;T;T;T;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;