16-58523396-C-G
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_016284.5(CNOT1):āc.6891G>Cā(p.Thr2297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,611,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000018 ( 0 hom. )
Consequence
CNOT1
NM_016284.5 synonymous
NM_016284.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0860
Genes affected
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 16-58523396-C-G is Benign according to our data. Variant chr16-58523396-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2176286.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000178 (26/1459112) while in subpopulation MID AF= 0.000174 (1/5750). AF 95% confidence interval is 0.0000109. There are 0 homozygotes in gnomad4_exome. There are 9 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNOT1 | NM_016284.5 | c.6891G>C | p.Thr2297= | synonymous_variant | 47/49 | ENST00000317147.10 | |
SETD6 | NM_001160305.4 | c.*4367C>G | 3_prime_UTR_variant | 8/8 | ENST00000219315.9 | ||
CNOT1 | NM_001265612.2 | c.6876G>C | p.Thr2292= | synonymous_variant | 47/49 | ||
CNOT1 | NR_049763.2 | n.7332G>C | non_coding_transcript_exon_variant | 48/50 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNOT1 | ENST00000317147.10 | c.6891G>C | p.Thr2297= | synonymous_variant | 47/49 | 1 | NM_016284.5 | P3 | |
SETD6 | ENST00000219315.9 | c.*4367C>G | 3_prime_UTR_variant | 8/8 | 1 | NM_001160305.4 | |||
ENST00000622896.1 | n.427C>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250982Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135668
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459112Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 725860
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 03, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at