Variant 3-328192-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006614.4(CHL1):c.223C>A(p.Pro75Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CHL1
NM_006614.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20718434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4 linkuse as main transcript	c.223C>A	p.Pro75Thr	missense_variant	5/28	ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7 linkuse as main transcript	c.223C>A	p.Pro75Thr	missense_variant	5/28	1	NM_006614.4	P3	O00533-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452098

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

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

Apr 26, 2024

The c.223C>A (p.P75T) alteration is located in exon 5 (coding exon 3) of the CHL1 gene. This alteration results from a C to A substitution at nucleotide position 223, causing the proline (P) at amino acid position 75 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.052

.;T;.;.;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.57

T;T;T;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.21

T;T;T;T;T;T

MetaSVM

Uncertain

0.60

MutationTaster

Benign

0.57

D;D

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.85

N;N;N;N;N;.

REVEL

Benign

0.20

Sift

Benign

0.079

T;T;T;T;T;.

Sift4G

Benign

0.39

T;T;T;T;T;T

Polyphen

0.27

B;B;.;.;.;.

Vest4

0.16

MutPred

0.46

Gain of glycosylation at T70 (P = 0.0364);Gain of glycosylation at T70 (P = 0.0364);Gain of glycosylation at T70 (P = 0.0364);Gain of glycosylation at T70 (P = 0.0364);Gain of glycosylation at T70 (P = 0.0364);Gain of glycosylation at T70 (P = 0.0364);

MVP

0.62

MPC

0.012

ClinPred

0.21

GERP RS

3.0

Varity_R

0.067

gMVP

0.52

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