X-44873369-T-TGCCGCC

Variant names:

• chrX-44873369-T-TGCCGCC
• rs762577042
• NM_001291415.2:c.-170_-165dupGCCGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001291415.2(KDM6A):​c.-170_-165dupGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., 112 hem., cov: 18)
  • Exomes 𝑓: 0.0047 (7 hom. 586 hem.)
• Consequence: KDM6A NM_001291415.2 5_prime_UTR
• Clinical Significance: Likely 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-TGCCGCC is Benign according to our data. Variant chrX-44873369-T-TGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 1198356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00401 (426/106173) while in subpopulation NFE AF= 0.00544 (280/51424). AF 95% confidence interval is 0.00492. There are 3 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2	c.-170_-165dupGCCGCC		5_prime_UTR_variant	Exon 1 of 30	ENST00000611820.5	NP_001278344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820	c.-170_-165dupGCCGCC		5_prime_UTR_variant	Exon 1 of 30	1	NM_001291415.2	ENSP00000483595.2

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 426 AN: 106141 Hom.: 3 Cov.: 18 AF XY: 0.00375 AC XY: 112 AN XY: 29861

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00307

Gnomad AMR AF: 0.000885

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000855

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.00210

GnomAD4 exome AF: 0.00475 AC: 2185 AN: 460185 Hom.: 7 Cov.: 8 AF XY: 0.00513 AC XY: 586 AN XY: 114205

Gnomad4 AFR exome AF: 0.000796

Gnomad4 AMR exome AF: 0.000922

Gnomad4 ASJ exome AF: 0.000113

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.000619

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.00417

Gnomad4 OTH exome AF: 0.00432

GnomAD4 genome AF: 0.00401 AC: 426 AN: 106173 Hom.: 3 Cov.: 18 AF XY: 0.00375 AC XY: 112 AN XY: 29903

Gnomad4 AFR AF: 0.00121

Gnomad4 AMR AF: 0.000884

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000858

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.00544

Gnomad4 OTH AF: 0.00208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;