NM_001291415.2:c.385-14107G>C

Variant names:

• chrX-44996854-G-C
• rs9781530
• NM_001291415.2:c.385-14107G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291415.2(KDM6A):​c.385-14107G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 111,068 control chromosomes in the GnomAD database, including 4,571 homozygotes. There are 6,841 hemizygotes in GnomAD. 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 0.22 (4571 hom., 6841 hem., cov: 22)
• Consequence: KDM6A NM_001291415.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.385-14107G>C		intron_variant	Intron 4 of 29	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820.5	c.385-14107G>C		intron_variant	Intron 4 of 29	1	NM_001291415.2	ENSP00000483595.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 24682 AN: 111012 Hom.: 4560 Cov.: 22 AF XY: 0.205 AC XY: 6808 AN XY: 33258

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.00726

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.223 AC: 24733 AN: 111068 Hom.: 4571 Cov.: 22 AF XY: 0.205 AC XY: 6841 AN XY: 33324

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0606

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.195

Alfa AF: 0.0428 Hom.: 222

Bravo AF: 0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.26

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

LitVar

Other links and lift over

dbSNP: rs9781530; hg19: chrX-44856099;