X-44873502-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001291415.2(KDM6A):c.-50C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,204,396 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., 22 hem., cov: 23)
  • Exomes 𝑓: 0.000054 (0 hom. 9 hem.)
• Consequence: KDM6A NM_001291415.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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=-0.4).
• BP6: Variant X-44873502-C-G is Benign according to our data. Variant chrX-44873502-C-G is described in ClinVar as [Benign]. Clinvar id is 1290124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00056 (62/110632) while in subpopulation AFR AF= 0.0019 (58/30450). AF 95% confidence interval is 0.00151. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6A	NM_001291415.2	c.-50C>G		5_prime_UTR_variant	1/30	ENST00000611820.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6A	ENST00000611820.5	c.-50C>G		5_prime_UTR_variant	1/30	1	NM_001291415.2	P4

Frequencies

GnomAD3 genomes AF: 0.000561 AC: 62 AN: 110579 Hom.: 0 Cov.: 23 AF XY: 0.000665 AC XY: 22 AN XY: 33061

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000377

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000126 AC: 22 AN: 175125 Hom.: 0 AF XY: 0.0000620 AC XY: 4 AN XY: 64525

Gnomad AFR exome AF: 0.00180

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000137

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000539 AC: 59 AN: 1093764 Hom.: 0 Cov.: 31 AF XY: 0.0000250 AC XY: 9 AN XY: 360298

Gnomad4 AFR exome AF: 0.00194

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000131

GnomAD4 genome AF: 0.000560 AC: 62 AN: 110632 Hom.: 0 Cov.: 23 AF XY: 0.000664 AC XY: 22 AN XY: 33118

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.000377

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000925 Hom.: 4

Bravo AF: 0.000646

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 19, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	8.2
Dann	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs768056637; hg19: chrX-44732748;