chr5-138352808-G-A

Position:

chr5-138352808-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2

The NM_016604.4(KDM3B):c.13G>A(p.Ala5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 1,306,040 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 59 hom., cov: 32)

Exomes 𝑓: 0.031 ( 696 hom. )

Consequence

KDM3B
NM_016604.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015516281).

BP6

Variant 5-138352808-G-A is Benign according to our data. Variant chr5-138352808-G-A is described in ClinVar as [Benign]. Clinvar id is 3055328.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0225 (3400/151256) while in subpopulation NFE AF= 0.0319 (2158/67630). AF 95% confidence interval is 0.0308. There are 59 homozygotes in gnomad4. There are 1684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/24	ENST00000314358.10	NP_057688.3	Q7LBC6-1
KDM3B	XM_005272018.5 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/23		XP_005272075.1
KDM3B	XM_047417313.1 linkuse as main transcript	c.-1036G>A		5_prime_UTR_variant	1/25		XP_047273269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10 linkuse as main transcript	c.13G>A	p.Ala5Thr	missense_variant	1/24	1	NM_016604.4	ENSP00000326563.5		Q7LBC6-1

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3400

AN:

151148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0251

GnomAD3 exomes

AF:

0.0251

AC:

700

AN:

27918

Hom.:

AF XY:

0.0258

AC XY:

440

AN XY:

17070

show subpopulations

Gnomad AFR exome

AF:

0.00248

Gnomad AMR exome

AF:

0.00935

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.0508

Gnomad NFE exome

AF:

0.0329

Gnomad OTH exome

AF:

0.0266

GnomAD4 exome

AF:

0.0314

AC:

36276

AN:

1154784

Hom.:

696

Cov.:

AF XY:

0.0314

AC XY:

17682

AN XY:

562976

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.0000825

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0599

Gnomad4 NFE exome

AF:

0.0334

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0225

AC:

3400

AN:

151256

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

1684

AN XY:

73920

show subpopulations

Gnomad4 AFR

AF:

0.00463

Gnomad4 AMR

AF:

0.0174

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0190

Gnomad4 FIN

AF:

0.0541

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0248

Alfa

AF:

0.0314

Hom.:

Bravo

AF:

0.0187

ExAC

AF:

0.0138

AC:

169

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KDM3B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.40

REVEL

Benign

0.10

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.11

MPC

0.55

ClinPred

0.058

GERP RS

3.8

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.1

Varity_R

0.31

gMVP

0.41

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over