dbSNP rs376640941: CHADL:p.Asp671Tyr (chr22-41236536-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_138481.2(CHADL):c.2011G>T(p.Asp671Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,551,444 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D671N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CHADL
NM_138481.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.95

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:

Genome browser will be placed here

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=0.09949502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHADL	NM_138481.2 link	c.2011G>T	p.Asp671Tyr	missense_variant	Exon 4 of 6	ENST00000216241.14	NP_612490.1	Q6NUI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHADL	ENST00000216241.14 link	c.2011G>T	p.Asp671Tyr	missense_variant	Exon 4 of 6	1	NM_138481.2	ENSP00000216241.9	Q6NUI6-1
CHADL	ENST00000455425.1 link	c.502G>T	p.Asp168Tyr	missense_variant	Exon 3 of 4	2		ENSP00000412359.1	B0QYT2
CHADL	ENST00000417999.5 link	c.1973+29G>T		intron_variant	Intron 3 of 4	5		ENSP00000392046.1	H0Y4I5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000130

AC:

AN:

153958

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81732

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

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:

7.15e-7

AC:

AN:

1399136

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

AF:

0.00000657

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000674

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.89

L;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.016

D;.

Polyphen

1.0

D;.

Vest4

0.44

MutPred

0.49

Loss of disorder (P = 0.0294);.;

MVP

0.57

MPC

0.20

ClinPred

0.96

GERP RS

4.0

Varity_R

0.21

gMVP

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over