11-90211265-T-C

Variant names:

• chr11-90211265-T-C
• NM_012124.3:c.383A>G

Variant summary

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

The NM_012124.3(CHORDC1):​c.383A>G​(p.Gln128Arg) 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: 6.50

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=0.21782458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHORDC1	NM_012124.3	c.383A>G	p.Gln128Arg	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.383A>G	p.Gln128Arg	missense_variant	Exon 5 of 11	1	NM_012124.3	ENSP00000319255.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.383A>G (p.Q128R) alteration is located in exon 5 (coding exon 5) of the CHORDC1 gene. This alteration results from a A to G substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by an arginine (R). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.14	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.11	B;B
Vest4		0.50
MutPred		0.26		Gain of MoRF binding (P = 0.0149);.;
MVP		0.46
MPC		0.14
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-89944433;