Genetic Variant NM_012124.3:c.102C>G (chr11-90218147-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012124.3(CHORDC1):c.102C>G(p.His34Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000388 in 1,573,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

CHORDC1
NM_012124.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Publications

2 publications found

Variant links:

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]

CHORDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.916

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012124.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHORDC1	NM_012124.3	MANE Select	c.102C>G	p.His34Gln	missense	Exon 2 of 11	NP_036256.2	Q9UHD1-1
	CHORDC1	NM_001144073.2		c.102C>G	p.His34Gln	missense	Exon 2 of 10	NP_001137545.1	Q9UHD1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHORDC1	ENST00000320585.11	TSL:1 MANE Select	c.102C>G	p.His34Gln	missense	Exon 2 of 11	ENSP00000319255.6	Q9UHD1-1
CHORDC1	ENST00000457199.6	TSL:1	c.102C>G	p.His34Gln	missense	Exon 2 of 10	ENSP00000401080.2	Q9UHD1-2
CHORDC1	ENST00000907759.1		c.102C>G	p.His34Gln	missense	Exon 2 of 10	ENSP00000577818.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151354

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000235

AC:

AN:

212912

AF XY:

0.0000346

show subpopulations

Gnomad AFR exome

AF:

0.0000699

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.0000408

AC:

AN:

1422430

Hom.:

Cov.:

AF XY:

0.0000382

AC XY:

AN XY:

707146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30356

American (AMR)

AF:

0.0000285

AC:

AN:

35044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

38068

South Asian (SAS)

AF:

0.00

AC:

AN:

78802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.0000510

AC:

AN:

1098048

Other (OTH)

AF:

0.0000170

AC:

AN:

58696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151354

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73822

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41130

American (AMR)

AF:

0.00

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67926

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000460

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.22

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Pathogenic

0.85

Eigen

Benign

0.023

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.085

MutationAssessor

Pathogenic

3.7

PhyloP100

2.3

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.90

MutPred

0.94

Gain of helix (P = 0.0696)

MVP

0.79

MPC

0.59

ClinPred

0.86

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.79

Mutation Taster

=9/91

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over