Genetic Variant KDM5C:c.*124G>T (chrX-53192843-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146702.2(KDM5C):c.4047-6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 18)

Exomes 𝑓: 0.0000021 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

KDM5C
NM_001146702.2 splice_region, intron

Scores

Splicing: ADA: 0.000009886

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.911

Publications

0 publications found

Variant links:

Genes affected

KDM5C (HGNC:11114): (lysine demethylase 5C) This gene is a member of the SMCY homolog family and encodes a protein with one ARID domain, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. Mutations in this gene have been associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KDM5C Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability Claes-Jensen type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

KDM5C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146702.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5C	NM_004187.5	MANE Select	c.*124G>T	3_prime_UTR	Exon 26 of 26	NP_004178.2	P41229-1
KDM5C	NM_001282622.3		c.*124G>T	3_prime_UTR	Exon 26 of 26	NP_001269551.1	P41229-5
KDM5C	NM_001353978.3		c.*124G>T	3_prime_UTR	Exon 26 of 26	NP_001340907.1	P41229-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDM5C	ENST00000375401.8	TSL:1 MANE Select	c.*124G>T	3_prime_UTR	Exon 26 of 26	ENSP00000364550.4	P41229-1
KDM5C	ENST00000404049.7	TSL:1	c.*124G>T	3_prime_UTR	Exon 26 of 26	ENSP00000385394.3	P41229-5
KDM5C	ENST00000935430.1		c.*124G>T	3_prime_UTR	Exon 27 of 27	ENSP00000605489.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

88593

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000211

AC:

AN:

473175

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

127167

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12588

American (AMR)

AF:

0.00

AC:

AN:

20543

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10525

East Asian (EAS)

AF:

0.00

AC:

AN:

15367

South Asian (SAS)

AF:

0.00

AC:

AN:

35270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24923

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1761

European-Non Finnish (NFE)

AF:

0.00000302

AC:

AN:

331543

Other (OTH)

AF:

0.00

AC:

AN:

20655

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

88668

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

18594

African (AFR)

AF:

0.00

AC:

AN:

25470

American (AMR)

AF:

0.00

AC:

AN:

7666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2302

East Asian (EAS)

AF:

0.00

AC:

AN:

2063

South Asian (SAS)

AF:

0.00

AC:

AN:

1242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

45161

Other (OTH)

AF:

0.00

AC:

AN:

1230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.2

(source)

DANN

Benign

0.59

PhyloP100

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000099

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over