Variant 16-58523305-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001160305.4(SETD6):c.*4286dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,315,178 control chromosomes in the GnomAD database, including 30,548 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12571 hom., cov: 0)

Exomes 𝑓: 0.28 ( 17977 hom. )

Consequence

SETD6
NM_001160305.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270

Variant links:

Genes affected

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 links:

CNOT1 (HGNC:7877): (CCR4-NOT transcription complex subunit 1) Enables armadillo repeat domain binding activity; molecular adaptor activity; and nuclear receptor binding activity. Contributes to poly(A)-specific ribonuclease activity. Involved in several processes, including negative regulation of signal transduction; positive regulation of cytoplasmic mRNA processing body assembly; and regulation of gene expression. Located in P-body and cytosol. Part of CCR4-NOT complex. Implicated in holoprosencephaly. [provided by Alliance of Genome Resources, Apr 2022]

CNOT1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-58523305-G-GA is Benign according to our data. Variant chr16-58523305-G-GA is described in ClinVar as [Benign]. Clinvar id is 1277952.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SETD6	NM_001160305.4 linkuse as main transcript	c.*4286dup	3_prime_UTR_variant	8/8	ENST00000219315.9	NP_001153777.1
CNOT1	NM_016284.5 linkuse as main transcript	c.6917+64_6917+65insT	intron_variant		ENST00000317147.10	NP_057368.3
CNOT1	NM_001265612.2 linkuse as main transcript	c.6902+64_6902+65insT	intron_variant			NP_001252541.1
CNOT1	NR_049763.2 linkuse as main transcript	n.7358+64_7358+65insT	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD6	ENST00000219315.9 linkuse as main transcript	c.*4286dup	3_prime_UTR_variant	8/8	1	NM_001160305.4	ENSP00000219315		Q8TBK2-1
CNOT1	ENST00000317147.10 linkuse as main transcript	c.6917+64_6917+65insT	intron_variant		1	NM_016284.5	ENSP00000320949	P3	A5YKK6-1
	ENST00000622896.1 linkuse as main transcript	n.346dup	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

58194

AN:

148420

Hom.:

12558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.573

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.284

AC:

331122

AN:

1166660

Hom.:

17977

Cov.:

AF XY:

0.285

AC XY:

163940

AN XY:

575224

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.392

AC:

58243

AN:

148518

Hom.:

12571

Cov.:

AF XY:

0.393

AC XY:

28435

AN XY:

72328

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.573

Gnomad4 SAS

AF:

0.429

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.387

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over