16-58520876-C-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52
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]
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]

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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
SETD6NM_001160305.4 linkuse as main transcriptc.*1847C>T 3_prime_UTR_variant 8/8 ENST00000219315.9 NP_001153777.1
CNOT1NM_016284.5 linkuse as main transcriptc.*82G>A 3_prime_UTR_variant 49/49 ENST00000317147.10 NP_057368.3
CNOT1NM_001265612.2 linkuse as main transcriptc.*82G>A 3_prime_UTR_variant 49/49 NP_001252541.1
CNOT1NR_049763.2 linkuse as main transcriptn.7654G>A non_coding_transcript_exon_variant 50/50

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETD6ENST00000219315.9 linkuse as main transcriptc.*1847C>T 3_prime_UTR_variant 8/81 NM_001160305.4 ENSP00000219315 Q8TBK2-1
CNOT1ENST00000317147.10 linkuse as main transcriptc.*82G>A 3_prime_UTR_variant 49/491 NM_016284.5 ENSP00000320949 P3A5YKK6-1

Frequencies

GnomAD3 genomes
AF:
0.0503
AC:
7653
AN:
152180
Hom.:
263
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0126
Gnomad AMI
AF:
0.0592
Gnomad AMR
AF:
0.0480
Gnomad ASJ
AF:
0.0876
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0769
Gnomad FIN
AF:
0.0655
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.0707
Gnomad OTH
AF:
0.0636
GnomAD4 exome
AF:
0.0658
AC:
83106
AN:
1263916
Hom.:
3126
Cov.:
18
AF XY:
0.0668
AC XY:
42568
AN XY:
636944
show subpopulations
Gnomad4 AFR exome
AF:
0.0112
Gnomad4 AMR exome
AF:
0.0397
Gnomad4 ASJ exome
AF:
0.0932
Gnomad4 EAS exome
AF:
0.000206
Gnomad4 SAS exome
AF:
0.0864
Gnomad4 FIN exome
AF:
0.0634
Gnomad4 NFE exome
AF:
0.0687
Gnomad4 OTH exome
AF:
0.0677
GnomAD4 genome
AF:
0.0502
AC:
7650
AN:
152298
Hom.:
263
Cov.:
32
AF XY:
0.0503
AC XY:
3747
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0126
Gnomad4 AMR
AF:
0.0480
Gnomad4 ASJ
AF:
0.0876
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.0769
Gnomad4 FIN
AF:
0.0655
Gnomad4 NFE
AF:
0.0707
Gnomad4 OTH
AF:
0.0630
Alfa
AF:
0.0599
Hom.:
103
Bravo
AF:
0.0458
Asia WGS
AF:
0.0260
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
13
DANN
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs17821549; hg19: chr16-58554780; COSMIC: COSV54700103; COSMIC: COSV54700103; API