ENST00000692609.3:n.165C>G

Variant names:

• chr16-58515300-G-C
• rs1646010
• ENST00000692609.3:n.165C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000692609.3(ENSG00000289004):​n.165C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,216 control chromosomes in the GnomAD database, including 5,089 homozygotes. 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 0.25 (5089 hom., cov: 33)
• Consequence: ENSG00000289004 ENST00000692609.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 8 publications found

Genes affected

ENSG00000289004 (HGNC:):

NDRG4 (HGNC:14466): (NDRG family member 4) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.[provided by RefSeq, Jun 2011]

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SETD6 Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD6	NM_001160305.4	c.-238G>C		upstream_gene_variant		ENST00000219315.9	NP_001153777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD6	ENST00000219315.9	c.-238G>C		upstream_gene_variant		1	NM_001160305.4	ENSP00000219315.5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37643 AN: 152098 Hom.: 5074 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37684 AN: 152216 Hom.: 5089 Cov.: 33 AF XY: 0.253 AC XY: 18846 AN XY: 74424

African (AFR) AF: 0.159 AC: 6608 AN: 41548

American (AMR) AF: 0.351 AC: 5372 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1977 AN: 5166

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4822

European-Finnish (FIN) AF: 0.294 AC: 3111 AN: 10598

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17279 AN: 67992

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.257 Hom.: 658

Bravo AF: 0.247

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.9
DANN	Benign	0.64
PhyloP100		0.50
PromoterAI		-0.013	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1646010; hg19: chr16-58549204; COSMIC: COSV50748347;