Variant chr3-325973-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006614.4(CHL1):c.106A>G(p.Thr36Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,608,952 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

Variant links:

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

CHL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4 link	c.106A>G	p.Thr36Ala	missense_variant	4/28	ENST00000256509.7	NP_006605.2	O00533-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7 link	c.106A>G	p.Thr36Ala	missense_variant	4/28	1	NM_006614.4	ENSP00000256509.2		O00533-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

249224

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.000745

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1456752

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

724840

show subpopulations

Gnomad4 AFR exome

AF:

0.000421

Gnomad4 AMR exome

AF:

0.0000677

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000158

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.106A>G (p.T36A) alteration is located in exon 4 (coding exon 2) of the CHL1 gene. This alteration results from a A to G substitution at nucleotide position 106, causing the threonine (T) at amino acid position 36 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.;.;.;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D;T;D;D;D

M_CAP

Pathogenic

0.64

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.3

D;D;D;D;D;D;.

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0010

D;D;D;D;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D

Polyphen

1.0

D;D;.;.;.;.;.

Vest4

0.56

MVP

0.85

MPC

0.041

ClinPred

0.55

GERP RS

5.8

Varity_R

0.58

gMVP

0.67

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