X-110688628-T-G

Variant names:

• chrX-110688628-T-G
• rs5943053
• NM_001143981.2:c.954A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001143981.2(CHRDL1):​c.954A>C​(p.Lys318Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 22)
• Consequence: CHRDL1 NM_001143981.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRDL1	NM_001143981.2	c.954A>C	p.Lys318Asn	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.954A>C	p.Lys318Asn	missense_variant	Exon 9 of 12	2	NM_001143981.2	ENSP00000361112.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.;.
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.91	D;D;D;D;D
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Pathogenic	3.2	M;.;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	N;N;D;D;N
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.75
MutPred		0.58		Loss of methylation at K311 (P = 0.0021);.;.;.;.;
MVP		0.61
MPC		1.2
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.92
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs5943053; hg19: chrX-109931856;