Genetic Variant KDM6A:c.-167_-165dupGCC (chrX-44873369-T-TGCC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.304

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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 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 rank	MANE	Protein	UniProt
KDM6A	NM_001291415.2 link	c.-167_-165dupGCC		5_prime_UTR_variant	Exon 1 of 30	ENST00000611820.5	NP_001278344.1	A0A087X0R0B7ZKN5Q86TD1B7ZKN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6A	ENST00000611820 link	c.-167_-165dupGCC		5_prime_UTR_variant	Exon 1 of 30	1	NM_001291415.2	ENSP00000483595.2		A0A087X0R0

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

12697

AN:

106086

Hom.:

985

Cov.:

show subpopulations

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.:

AF XY:

0.0624

AC XY:

7047

AN XY:

112939

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

900

1800

2701

3601

4501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.120

AC:

12706

AN:

106118

Hom.:

988

Cov.:

AF XY:

0.0959

AC XY:

2867

AN XY:

29890

show subpopulations

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:

AN:

201

European-Non Finnish (NFE)

AF:

0.0647

AC:

3325

AN:

51412

Other (OTH)

AF:

0.111

AC:

160

AN:

1444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

375

750

1125

1500

1875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0243

Hom.:

Asia WGS

AF:

0.0950

AC:

239

AN:

2503

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

X-44873369-T-TGCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over