chr5-138352825-C-G

Position:

• chr5-138352825-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_016604.4(KDM3B):​c.30C>G​(p.Gly10Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000841 in 1,189,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: KDM3B NM_016604.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-138352825-C-G is Benign according to our data. Variant chr5-138352825-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.376 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM3B	NM_016604.4	c.30C>G	p.Gly10Gly	synonymous_variant	1/24	ENST00000314358.10	NP_057688.3
KDM3B	XM_005272018.5	c.30C>G	p.Gly10Gly	synonymous_variant	1/23		XP_005272075.1
KDM3B	XM_047417313.1	c.-1019C>G		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	c.30C>G	p.Gly10Gly	synonymous_variant	1/24	1	NM_016604.4	ENSP00000326563.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.41e-7 AC: 1 AN: 1189242 Hom.: 0 Cov.: 35 AF XY: 0.00000172 AC XY: 1 AN XY: 582698

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: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

KDM3B: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.88
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-137688514;