Genetic Variant CHORDC1:p.Thr303Ser (chr11-90202497-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012124.3(CHORDC1):c.907A>T(p.Thr303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CHORDC1
NM_012124.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.653

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 made for transcript

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=0.07624683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHORDC1	NM_012124.3 link	c.907A>T	p.Thr303Ser	missense_variant	Exon 11 of 11	ENST00000320585.11	NP_036256.2	Q9UHD1-1
CHORDC1	NM_001144073.2 link	c.850A>T	p.Thr284Ser	missense_variant	Exon 10 of 10		NP_001137545.1	Q9UHD1-2
CHORDC1	XM_017017541.3 link	c.565A>T	p.Thr189Ser	missense_variant	Exon 11 of 11		XP_016873030.1
CHORDC1	XM_047426766.1 link	c.565A>T	p.Thr189Ser	missense_variant	Exon 8 of 8		XP_047282722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHORDC1	ENST00000320585.11 link	c.907A>T	p.Thr303Ser	missense_variant	Exon 11 of 11	1	NM_012124.3	ENSP00000319255.6		Q9UHD1-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250888

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000158

AC:

231

AN:

1460830

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000201

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.907A>T (p.T303S) alteration is located in exon 11 (coding exon 11) of the CHORDC1 gene. This alteration results from a A to T substitution at nucleotide position 907, causing the threonine (T) at amino acid position 303 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

Benign

0.098

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.20

T;.;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.75

M_CAP

Benign

0.0046

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.78

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.085

MutPred

0.44

Gain of disorder (P = 0.0813);.;.;.;

MVP

0.23

MPC

0.11

ClinPred

0.048

GERP RS

-0.040

Varity_R

0.035

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over