Variant 22-41237331-G-T 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_138481.2(CHADL):c.1741C>A(p.Leu581Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,398,324 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHADL
NM_138481.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

Variant links:

Genes affected

CHADL (HGNC:25165): (chondroadherin like) Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

CHADL 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=0.09196532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHADL	NM_138481.2 linkuse as main transcript	c.1741C>A	p.Leu581Met	missense_variant	3/6	ENST00000216241.14	NP_612490.1	Q6NUI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHADL	ENST00000216241.14 linkuse as main transcript	c.1741C>A	p.Leu581Met	missense_variant	3/6	1	NM_138481.2	ENSP00000216241.9	Q6NUI6-1
CHADL	ENST00000417999.5 linkuse as main transcript	c.1732C>A	p.Leu578Met	missense_variant	2/5	5		ENSP00000392046.1	H0Y4I5
CHADL	ENST00000455425.1 linkuse as main transcript	c.232C>A	p.Leu78Met	missense_variant	2/4	2		ENSP00000412359.1	B0QYT2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

152992

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81620

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000922

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:

0.00000143

AC:

AN:

1398324

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000760

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

Oct 25, 2023

The c.1741C>A (p.L581M) alteration is located in exon 3 (coding exon 3) of the CHADL gene. This alteration results from a C to A substitution at nucleotide position 1741, causing the leucine (L) at amino acid position 581 to be replaced by a methionine (M). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.69

T;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.092

T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.92

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.41

Sift

Benign

0.064

T;D

Sift4G

Pathogenic

0.0

D;.

Polyphen

1.0

D;.

Vest4

0.49

MutPred

0.59

Gain of phosphorylation at T586 (P = 0.1073);.;

MVP

0.47

MPC

0.20

ClinPred

0.95

GERP RS

5.0

Varity_R

0.29

gMVP

0.38

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