X-110688641-T-G

Variant names:

• chrX-110688641-T-G
• NM_001143981.2:c.941A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001143981.2(CHRDL1):​c.941A>C​(p.Lys314Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CHRDL1 NM_001143981.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.66

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRDL1	NM_001143981.2	c.941A>C	p.Lys314Thr	missense_variant	Exon 9 of 12	ENST00000372042.6	NP_001137453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRDL1	ENST00000372042.6	c.941A>C	p.Lys314Thr	missense_variant	Exon 9 of 12	2	NM_001143981.2	ENSP00000361112.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097916 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363286

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.77	N;.;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.3	N;N;N;D;N
REVEL	Uncertain	0.58
Sift	Benign	0.051	T;D;D;D;D
Sift4G	Benign	0.065	T;T;T;T;T
Polyphen		1.0	D;.;.;.;.
Vest4		0.73
MutPred		0.55		Loss of methylation at K307 (P = 0.0128);.;.;.;.;
MVP		0.91
MPC		1.2
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.60
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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-109931869;