rs7706614

Variant names:

• chr5-138419119-G-A
• rs7706614
• NM_016604.4:c.3602G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (178 hom., cov: 30)
  • Exomes 𝑓: 0.036 (1345 hom.)
• Consequence: KDM3B NM_016604.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.68
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• Diets-Jongmans syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.3602G>A	p.Ser1201Asn	missense_variant	Exon 14 of 24	ENST00000314358.10	NP_057688.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6269 AN: 152140 Hom.: 175 Cov.: 30

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

GnomAD2 exomes AF: 0.0406 AC: 10198 AN: 251428 AF XY: 0.0441

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 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.: 33 AF XY: 0.0377 AC XY: 27396 AN XY: 727242

African (AFR) AF: 0.0608 AC: 2037 AN: 33480

American (AMR) AF: 0.0190 AC: 849 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 865 AN: 26136

East Asian (EAS) AF: 0.0106 AC: 422 AN: 39700

South Asian (SAS) AF: 0.103 AC: 8845 AN: 86258

European-Finnish (FIN) AF: 0.0302 AC: 1613 AN: 53420

Middle Eastern (MID) AF: 0.0409 AC: 236 AN: 5768

European-Non Finnish (NFE) AF: 0.0314 AC: 34899 AN: 1111998

Other (OTH) AF: 0.0376 AC: 2271 AN: 60396

GnomAD4 genome AF: 0.0413 AC: 6284 AN: 152258 Hom.: 178 Cov.: 30 AF XY: 0.0426 AC XY: 3170 AN XY: 74444

African (AFR) AF: 0.0593 AC: 2465 AN: 41536

American (AMR) AF: 0.0278 AC: 425 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3468

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5186

South Asian (SAS) AF: 0.110 AC: 532 AN: 4832

European-Finnish (FIN) AF: 0.0301 AC: 319 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0320 AC: 2178 AN: 68022

Other (OTH) AF: 0.0331 AC: 70 AN: 2112

Alfa AF: 0.0350 Hom.: 505

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

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	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0096	T;.
Eigen	Benign	-0.091
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;.
PhyloP100		3.7
PrimateAI	Benign	0.45	T
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	T
GERP RS		5.6
Varity_R		0.087
gMVP		0.26
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7706614; hg19: chr5-137754808;