dbSNP rs7706614: KDM3B:p.Ser1201Asn (chr5-138419119-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_016604.4(KDM3B):c.3602G>A(p.Ser1201Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0361 in 1,614,138 control chromosomes in the GnomAD database, including 1,523 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.041 ( 178 hom., cov: 30)

Exomes 𝑓: 0.036 ( 1345 hom. )

Consequence

KDM3B
NM_016604.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.68

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014431775).

BP6

Variant 5-138419119-G-A is Benign according to our data. Variant chr5-138419119-G-A is described in ClinVar as [Benign]. Clinvar id is 1302063.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM3B	NM_016604.4 link	c.3602G>A	p.Ser1201Asn	missense_variant	Exon 14 of 24	ENST00000314358.10	NP_057688.3	Q7LBC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM3B	ENST00000314358.10 link	c.3602G>A	p.Ser1201Asn	missense_variant	Exon 14 of 24	1	NM_016604.4	ENSP00000326563.5		Q7LBC6-1

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6269

AN:

152140

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0320

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0406

AC:

10198

AN:

251428

Hom.:

328

AF XY:

0.0441

AC XY:

5994

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.0295

Gnomad EAS exome

AF:

0.0116

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0349

Gnomad OTH exome

AF:

0.0378

GnomAD4 exome

AF:

0.0356

AC:

52037

AN:

1461880

Hom.:

1345

Cov.:

AF XY:

0.0377

AC XY:

27396

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0608

Gnomad4 AMR exome

AF:

0.0190

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0302

Gnomad4 NFE exome

AF:

0.0314

Gnomad4 OTH exome

AF:

0.0376

GnomAD4 genome

AF:

0.0413

AC:

6284

AN:

152258

Hom.:

178

Cov.:

AF XY:

0.0426

AC XY:

3170

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0593

Gnomad4 AMR

AF:

0.0278

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.0100

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0320

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0348

Hom.:

265

Bravo

AF:

0.0400

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0350

AC:

135

ESP6500AA

AF:

0.0549

AC:

242

ESP6500EA

AF:

0.0324

AC:

279

ExAC

AF:

0.0434

AC:

5269

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

EpiCase

AF:

0.0332

EpiControl

AF:

0.0376

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 28, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0096

T;.

Eigen

Benign

-0.091

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.60

N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.70

N;.

REVEL

Benign

0.060

Sift

Benign

0.14

T;.

Sift4G

Benign

0.52

T;T

Polyphen

0.0010

B;.

Vest4

0.094

MPC

0.53

ClinPred

0.0070

GERP RS

5.6

Varity_R

0.087

gMVP

0.26

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