dbSNP rs111692608: CNOT3:c.-59T>C (chr19-54142920-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001440655.1(CNOT3):c.-53-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CNOT3
NM_001440655.1 splice_region, intron

Scores

Splicing: ADA: 0.0003897

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.293

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT3	NM_014516.4 link	c.-50-9T>C		intron_variant	Intron 1 of 17	ENST00000221232.11	NP_055331.1	O75175A0A024R4R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT3	ENST00000221232.11 link	c.-50-9T>C		intron_variant	Intron 1 of 17	1	NM_014516.4	ENSP00000221232.5		O75175

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32632

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25864

East Asian (EAS)

AF:

0.00

AC:

AN:

39514

South Asian (SAS)

AF:

0.00

AC:

AN:

85406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1073730

Other (OTH)

AF:

0.00

AC:

AN:

59010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over