X-44873369-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCC

Variant names:

• chrX-44873369-T-TGCC
• rs762577042
• NM_001291415.2:c.-167_-165dupGCC

Variant summary

Our verdict is Benign. The variant received -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
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Kabuki syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291415.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	NM_001291415.2	MANE Select	c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 30	NP_001278344.1	A0A087X0R0
	KDM6A	NM_001419809.1		c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 31	NP_001406738.1
	KDM6A	NM_001419810.1		c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 30	NP_001406739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM6A	ENST00000611820.5	TSL:1 MANE Select	c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 30	ENSP00000483595.2	A0A087X0R0
	KDM6A	ENST00000382899.9	TSL:1	c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 29	ENSP00000372355.6	F8W8R6
	KDM6A	ENST00000377967.9	TSL:1	c.-167_-165dupGCC		5_prime_UTR	Exon 1 of 29	ENSP00000367203.4	O15550

Frequencies

GnomAD3 genomes AF: 0.120 AC: 12697 AN: 106086 Hom.: 985 Cov.: 18

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

African (AFR) AF: 0.246 AC: 2142 AN: 8701

American (AMR) AF: 0.0569 AC: 677 AN: 11898

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 569 AN: 8807

East Asian (EAS) AF: 0.0266 AC: 484 AN: 18229

South Asian (SAS) AF: 0.0982 AC: 2833 AN: 28851

European-Finnish (FIN) AF: 0.0391 AC: 1045 AN: 26730

Middle Eastern (MID) AF: 0.0940 AC: 131 AN: 1394

European-Non Finnish (NFE) AF: 0.0535 AC: 17773 AN: 332444

Other (OTH) AF: 0.0770 AC: 1668 AN: 21673

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

African (AFR) AF: 0.264 AC: 7619 AN: 28869

American (AMR) AF: 0.0845 AC: 860 AN: 10175

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 151 AN: 2591

East Asian (EAS) AF: 0.0422 AC: 132 AN: 3127

South Asian (SAS) AF: 0.121 AC: 282 AN: 2332

European-Finnish (FIN) AF: 0.0265 AC: 141 AN: 5315

Middle Eastern (MID) AF: 0.139 AC: 28 AN: 201

European-Non Finnish (NFE) AF: 0.0647 AC: 3325 AN: 51412

Other (OTH) AF: 0.111 AC: 160 AN: 1444

Alfa AF: 0.0243 Hom.: 99

Asia WGS AF: 0.0950 AC: 239 AN: 2503

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs762577042; hg19: chrX-44732615; COSMIC: COSV107480504; COSMIC: COSV107480504;