16-58520876-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_016284.5(CNOT1):c.*82G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,416,214 control chromosomes in the GnomAD database, including 3,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.050 ( 263 hom., cov: 32)
Exomes 𝑓: 0.066 ( 3126 hom. )
Consequence
CNOT1
NM_016284.5 3_prime_UTR
NM_016284.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.52
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]
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 16-58520876-C-T is Benign according to our data. Variant chr16-58520876-C-T is described in ClinVar as [Benign]. Clinvar id is 1289270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SETD6 | NM_001160305.4 | c.*1847C>T | 3_prime_UTR_variant | 8/8 | ENST00000219315.9 | NP_001153777.1 | ||
CNOT1 | NM_016284.5 | c.*82G>A | 3_prime_UTR_variant | 49/49 | ENST00000317147.10 | NP_057368.3 | ||
CNOT1 | NM_001265612.2 | c.*82G>A | 3_prime_UTR_variant | 49/49 | NP_001252541.1 | |||
CNOT1 | NR_049763.2 | n.7654G>A | non_coding_transcript_exon_variant | 50/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SETD6 | ENST00000219315.9 | c.*1847C>T | 3_prime_UTR_variant | 8/8 | 1 | NM_001160305.4 | ENSP00000219315 | |||
CNOT1 | ENST00000317147.10 | c.*82G>A | 3_prime_UTR_variant | 49/49 | 1 | NM_016284.5 | ENSP00000320949 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0503 AC: 7653AN: 152180Hom.: 263 Cov.: 32
GnomAD3 genomes
AF:
AC:
7653
AN:
152180
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0658 AC: 83106AN: 1263916Hom.: 3126 Cov.: 18 AF XY: 0.0668 AC XY: 42568AN XY: 636944
GnomAD4 exome
AF:
AC:
83106
AN:
1263916
Hom.:
Cov.:
18
AF XY:
AC XY:
42568
AN XY:
636944
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0502 AC: 7650AN: 152298Hom.: 263 Cov.: 32 AF XY: 0.0503 AC XY: 3747AN XY: 74462
GnomAD4 genome
AF:
AC:
7650
AN:
152298
Hom.:
Cov.:
32
AF XY:
AC XY:
3747
AN XY:
74462
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
89
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at