11-90211289-A-G

Variant names:

• chr11-90211289-A-G
• NM_012124.3:c.359T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012124.3(CHORDC1):​c.359T>C​(p.Leu120Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHORDC1 NM_012124.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

Genes affected

CHORDC1 (HGNC:14525): (cysteine and histidine rich domain containing 1) Enables Hsp90 protein binding activity. Predicted to be involved in centrosome duplication; chaperone-mediated protein folding; and regulation of cellular response to heat. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.11274117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHORDC1	NM_012124.3	c.359T>C	p.Leu120Ser	missense_variant	Exon 5 of 11	ENST00000320585.11	NP_036256.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHORDC1	ENST00000320585.11	c.359T>C	p.Leu120Ser	missense_variant	Exon 5 of 11	1	NM_012124.3	ENSP00000319255.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359T>C (p.L120S) alteration is located in exon 5 (coding exon 5) of the CHORDC1 gene. This alteration results from a T to C substitution at nucleotide position 359, causing the leucine (L) at amino acid position 120 to be replaced by a serine (S). 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	0.36
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	0.062
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.058
Sift	Benign	0.28	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.040	B;B
Vest4		0.26
MutPred		0.28		Gain of helix (P = 0.0225);.;
MVP		0.20
MPC		0.19
ClinPred		0.46	T
GERP RS		5.9
Varity_R		0.14
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr11-89944457;