X-44873369-T-TGCC

Position:

• chrX-44873369-T-TGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001291415.2(KDM6A):​c.-167_-165dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (988 hom., 2867 hem., cov: 18)
  • Exomes 𝑓: 0.060 (755 hom. 7047 hem.)
• Consequence: KDM6A NM_001291415.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.304

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 -10 ACMG points.

• BP6: Variant X-44873369-T-TGCC is Benign according to our data. Variant chrX-44873369-T-TGCC is described in ClinVar as [Benign]. Clinvar id is 1221796.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.-167_-165dupGCC		5_prime_UTR_variant	1/30	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820	c.-167_-165dupGCC		5_prime_UTR_variant	1/30	1	NM_001291415.2	ENSP00000483595.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 12697 AN: 106086 Hom.: 985 Cov.: 18 AF XY: 0.0958 AC XY: 2859 AN XY: 29848

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0123

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.0596 AC: 27322 AN: 458727 Hom.: 755 Cov.: 8 AF XY: 0.0624 AC XY: 7047 AN XY: 112939

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.0646

Gnomad4 EAS exome AF: 0.0266

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.0391

Gnomad4 NFE exome AF: 0.0535

Gnomad4 OTH exome AF: 0.0770

GnomAD4 genome AF: 0.120 AC: 12706 AN: 106118 Hom.: 988 Cov.: 18 AF XY: 0.0959 AC XY: 2867 AN XY: 29890

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.0845

Gnomad4 ASJ AF: 0.0583

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.111

Asia WGS AF: 0.0950 AC: 239 AN: 2503

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

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs762577042; hg19: chrX-44732615;