11-90202422-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012124.3(CHORDC1):​c.982G>T​(p.Asp328Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CHORDC1
NM_012124.3 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.158
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06611559).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHORDC1NM_012124.3 linkc.982G>T p.Asp328Tyr missense_variant Exon 11 of 11 ENST00000320585.11 NP_036256.2 Q9UHD1-1
CHORDC1NM_001144073.2 linkc.925G>T p.Asp309Tyr missense_variant Exon 10 of 10 NP_001137545.1 Q9UHD1-2
CHORDC1XM_017017541.3 linkc.640G>T p.Asp214Tyr missense_variant Exon 11 of 11 XP_016873030.1
CHORDC1XM_047426766.1 linkc.640G>T p.Asp214Tyr missense_variant Exon 8 of 8 XP_047282722.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHORDC1ENST00000320585.11 linkc.982G>T p.Asp328Tyr missense_variant Exon 11 of 11 1 NM_012124.3 ENSP00000319255.6 Q9UHD1-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000439
AC:
11
AN:
250850
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135568
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1459386
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
725994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.982G>T (p.D328Y) alteration is located in exon 11 (coding exon 11) of the CHORDC1 gene. This alteration results from a G to T substitution at nucleotide position 982, causing the aspartic acid (D) at amino acid position 328 to be replaced by a tyrosine (Y). 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
0.12
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.49
T;.;.;.
Eigen
Benign
-0.072
Eigen_PC
Benign
-0.042
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.066
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-2.9
D;D;D;D
REVEL
Benign
0.069
Sift
Uncertain
0.0080
D;D;D;D
Sift4G
Uncertain
0.017
D;D;D;D
Polyphen
0.86
P;.;P;.
Vest4
0.10
MutPred
0.25
Gain of helix (P = 0.0164);.;.;.;
MVP
0.19
MPC
0.28
ClinPred
0.26
T
GERP RS
3.4
Varity_R
0.17
gMVP
0.20

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.

Other links and lift over

dbSNP: rs745911071; hg19: chr11-89935590; API