Genetic Variant CNOT3:c.*5G>A (chr19-54155412-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014516.4(CNOT3):c.*5G>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 0.000154 in 1,578,442 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 (no stars).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

CNOT3
NM_014516.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

CNOT3 (HGNC:7879): (CCR4-NOT transcription complex subunit 3) Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CNOT3 links:

LENG1 (HGNC:15502): (leukocyte receptor cluster member 1)

LENG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-54155412-G-A is Benign according to our data. Variant chr19-54155412-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3056712.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000886 (135/152336) while in subpopulation AFR AF= 0.00305 (127/41590). AF 95% confidence interval is 0.00262. There are 0 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 135 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT3	NM_014516.4 link	c.*5G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000221232.11	NP_055331.1	O75175A0A024R4R3
LENG1	NM_024316.3 link	c.*309C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000222224.4	NP_077292.2	Q96BZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT3	ENST00000221232.11 link	c.*5G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_014516.4	ENSP00000221232.5		O75175
LENG1	ENST00000222224 link	c.*309C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_024316.3	ENSP00000222224.3		Q96BZ8

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000272

AC:

AN:

213280

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

115458

show subpopulations

Gnomad AFR exome

AF:

0.00244

Gnomad AMR exome

AF:

0.0000958

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00116

Gnomad SAS exome

AF:

0.0000740

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000323

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000757

AC:

108

AN:

1426106

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

709304

show subpopulations

Gnomad4 AFR exome

AF:

0.00199

Gnomad4 AMR exome

AF:

0.000141

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.000339

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000828

Gnomad4 OTH exome

AF:

0.000169

GnomAD4 genome

AF:

0.000886

AC:

135

AN:

152336

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00305

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000434

Hom.:

Bravo

AF:

0.000986

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNOT3-related disorder

Benign:1

Apr 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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