Genetic Variant NM_006618.5:c.4362G>C (chr1-202729842-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006618.5(KDM5B):c.4362G>C(p.Glu1454Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E1454E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

KDM5B
NM_006618.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

0 publications found

Variant links:

Genes affected

KDM5B (HGNC:18039): (lysine demethylase 5B) This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

KDM5B Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 65
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
intellectual disability
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

KDM5B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15116248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM5B	NM_006618.5	MANE Select	c.4362G>C	p.Glu1454Asp	missense	Exon 26 of 27	NP_006609.3
KDM5B	NM_001314042.2		c.4470G>C	p.Glu1490Asp	missense	Exon 27 of 28	NP_001300971.1	Q9UGL1-2
KDM5B	NM_001399817.1		c.4347G>C	p.Glu1449Asp	missense	Exon 26 of 27	NP_001386746.1	A0A3B3IS40

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KDM5B	ENST00000367265.9	TSL:1 MANE Select	c.4362G>C	p.Glu1454Asp	missense	Exon 26 of 27	ENSP00000356234.3	Q9UGL1-1
KDM5B	ENST00000367264.7	TSL:1	c.4470G>C	p.Glu1490Asp	missense	Exon 27 of 28	ENSP00000356233.2	Q9UGL1-2
KDM5B	ENST00000472822.6	TSL:1	n.1368G>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

M_CAP

Benign

0.036

MetaRNN

Benign

0.15

MetaSVM

Uncertain

-0.047

MutationAssessor

Benign

0.97

PhyloP100

1.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.32

Sift

Benign

0.098

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.23

MutPred

0.14

Gain of MoRF binding (P = 0.1167)

MVP

0.58

MPC

0.20

ClinPred

0.59

GERP RS

-0.69

PromoterAI

-0.0025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over