X-110688653-T-A

Variant summary

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

The NM_001143981.2(CHRDL1):c.929A>T(p.Lys310Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: CHRDL1 NM_001143981.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

Genes affected

CHRDL1 (HGNC:29861): (chordin like 1) This gene encodes an antagonist of bone morphogenetic protein 4. The encoded protein may play a role in topographic retinotectal projection and in the regulation of retinal angiogenesis in response to hypoxia. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

ACMG classification

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	UniProt
CHRDL1	NM_001143981.2	c.929A>T	p.Lys310Met	missense_variant	9/12	ENST00000372042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRDL1	ENST00000372042.6	c.929A>T	p.Lys310Met	missense_variant	9/12	2	NM_001143981.2	A1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

CHRDL1: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	0.0047	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.;.;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.6	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.015	D;D;D;D;D
Sift4G	Benign	0.063	T;T;T;T;T
Polyphen		1.0	D;.;.;.;.
Vest4		0.45
MutPred		0.62		Loss of methylation at K303 (P = 9e-04);.;.;.;.;
MVP		0.59
MPC		1.3
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.64
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-109931881;