Genetic Variant LENG1:c.*430C>A (chr19-54155291-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024316.3(LENG1):c.*430C>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 0.000000685 in 1,459,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LENG1
NM_024316.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760

Publications

0 publications found

Variant links:

Genes affected

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

LENG1 links:

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual developmental disorder with speech delay, autism, and dysmorphic facies
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

CNOT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08353144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG1	NM_024316.3 link	c.*430C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000222224.4	NP_077292.2	Q96BZ8
CNOT3	NM_014516.4 link	c.2164-18G>T		intron_variant	Intron 17 of 17	ENST00000221232.11	NP_055331.1	O75175A0A024R4R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LENG1	ENST00000222224.4 link	c.*430C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_024316.3	ENSP00000222224.3		Q96BZ8
CNOT3	ENST00000221232.11 link	c.2164-18G>T		intron_variant	Intron 17 of 17	1	NM_014516.4	ENSP00000221232.5		O75175

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726094

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111340

Other (OTH)

AF:

0.00

AC:

AN:

60336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.5

(source)

DANN

Benign

0.85

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.27

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

PhyloP100

-0.076

PROVEAN

Benign

-0.010

REVEL

Benign

0.10

Sift

Benign

0.77

Sift4G

Benign

1.0

MutPred

0.29

Gain of disorder (P = 0.0202);

MVP

0.28

ClinPred

0.10

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over