16-27203663-G-C

Position:

• chr16-27203663-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000286096.9(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 ENST00000286096.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM8	NM_024773.3	c.-32+27G>C		intron_variant		ENST00000286096.9	NP_079049.2
KDM8	XM_017023676.2	c.-32+27G>C		intron_variant			XP_016879165.1
KDM8	XM_047434654.1	c.-32+27G>C		intron_variant			XP_047290610.1
KDM8	XM_047434655.1	c.-32+27G>C		intron_variant			XP_047290611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM8	ENST00000286096.9	c.-32+27G>C		intron_variant		1	NM_024773.3	ENSP00000286096	P1
KDM8	ENST00000564961.1	n.129+27G>C		intron_variant, non_coding_transcript_variant		1
KDM8	ENST00000562269.1	n.120+27G>C		intron_variant, non_coding_transcript_variant		3

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

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: 0.00105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00293

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

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000564

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000774 Hom.: 13

Bravo AF: 0.00129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.89
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs16976587; hg19: chr16-27214984;