chr16-27203663-G-C

Variant names:

• chr16-27203663-G-C
• rs16976587
• NM_024773.3:c.-32+27G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024773.3(KDM8):​c.-32+27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 164,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: KDM8 NM_024773.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 7 publications found

Genes affected

KDM8 (HGNC:25840): (lysine demethylase 8) This gene likely encodes a histone lysine demethylase. Studies of a similar protein in mouse indicate a potential role for this protein as a tumor suppressor. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024773.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM8	NM_024773.3	MANE Select	c.-32+27G>C		intron	N/A	NP_079049.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM8	ENST00000286096.9	TSL:1 MANE Select	c.-32+27G>C		intron	N/A	ENSP00000286096.5
	KDM8	ENST00000564961.1	TSL:1	n.129+27G>C		intron	N/A
	KDM8	ENST00000562269.1	TSL:3	n.120+27G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 191 AN: 152240 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00136 AC: 17 AN: 12482 Hom.: 0 Cov.: 0 AF XY: 0.00131 AC XY: 9 AN XY: 6892

African (AFR) AF: 0.00 AC: 0 AN: 388

American (AMR) AF: 0.00 AC: 0 AN: 640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 478

East Asian (EAS) AF: 0.00 AC: 0 AN: 554

South Asian (SAS) AF: 0.00105 AC: 2 AN: 1904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00178 AC: 13 AN: 7294

Other (OTH) AF: 0.00293 AC: 2 AN: 682

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152358 Hom.: 0 Cov.: 34 AF XY: 0.00119 AC XY: 89 AN XY: 74500

African (AFR) AF: 0.000313 AC: 13 AN: 41572

American (AMR) AF: 0.000457 AC: 7 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.000564 AC: 6 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.0000342 Hom.: 98

Bravo AF: 0.00129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.89
DANN	Benign	0.58
PhyloP100		-0.19
PromoterAI		-0.048	Neutral

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: rs16976587; hg19: chr16-27214984;