Variant 5-138375093-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_016604.4(KDM3B):c.361A>G(p.Thr121Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000141 in 1,414,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KDM3B
NM_016604.4 missense, splice_region

Scores

Splicing: ADA: 0.6123

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

KDM3B (HGNC:1337): (lysine demethylase 3B) Predicted to enable chromatin DNA binding activity; histone H3-methyl-lysine-9 demethylase activity; and transcription coregulator activity. Predicted to be involved in histone H3-K9 demethylation and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of acute lymphoblastic leukemia; breast cancer; colorectal cancer; and lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

KDM3B links:

KDM3B (HGNC:):

KDM3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KDM3B. . Gene score misZ 4.9789 (greater than the threshold 3.09). Trascript score misZ 6.2129 (greater than threshold 3.09). GenCC has associacion of gene with Diets-Jongmans syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4 linkuse as main transcript	c.361A>G	p.Thr121Ala	missense_variant, splice_region_variant	3/24	ENST00000314358.10	NP_057688.3	Q7LBC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDM3B	ENST00000314358.10 linkuse as main transcript	c.361A>G	p.Thr121Ala	missense_variant, splice_region_variant	3/24	1	NM_016604.4	ENSP00000326563.5	Q7LBC6-1
KDM3B	ENST00000510866.5 linkuse as main transcript	n.169A>G		splice_region_variant, non_coding_transcript_exon_variant	2/24	1		ENSP00000425186.1	H0Y9V5
KDM3B	ENST00000512928.1 linkuse as main transcript	n.50A>G		splice_region_variant, non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1414052

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KDM3B-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2023

The KDM3B c.361A>G variant is predicted to result in the amino acid substitution p.Thr121Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

REVEL

Benign

0.23

Sift

Benign

0.054

Sift4G

Benign

0.27

Polyphen

0.98

Vest4

0.48

MutPred

0.36

Loss of sheet (P = 0.0817);

MVP

0.55

MPC

0.76

ClinPred

0.75

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.61

dbscSNV1_RF

Benign

0.45

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over