NM_138477.4:c.386G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_138477.4(CDAN1):​c.386G>T​(p.Arg129Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CDAN1
NM_138477.4 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.741

Publications

2 publications found
Variant links:
Genes affected
CDAN1 (HGNC:1713): (codanin 1) This gene encodes a protein that appears to play a role in nuclear envelope integrity, possibly related to microtubule attachments. Mutations in this gene cause congenital dyserythropoietic anemia type I, a disease resulting in morphological and functional abnormalities of erythropoiesis. [provided by RefSeq, Jul 2009]
CDAN1 Gene-Disease associations (from GenCC):
  • anemia, congenital dyserythropoietic, type 1a
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • congenital dyserythropoietic anemia type 1
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital dyserythropoietic anemia
    Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27333194).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDAN1NM_138477.4 linkc.386G>T p.Arg129Leu missense_variant Exon 2 of 28 ENST00000356231.4 NP_612486.2 Q8IWY9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDAN1ENST00000356231.4 linkc.386G>T p.Arg129Leu missense_variant Exon 2 of 28 1 NM_138477.4 ENSP00000348564.3 Q8IWY9-2
CDAN1ENST00000643434.1 linkn.91-404G>T intron_variant Intron 1 of 24 ENSP00000494699.1 A0A2R8Y5C2
CDAN1ENST00000563260.1 linkc.*77G>T downstream_gene_variant 3 ENSP00000455536.1 H3BPZ6

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151940
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000169
AC:
1
AN:
59214
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000406
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000154
AC:
2
AN:
1295712
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
636472
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
25926
American (AMR)
AF:
0.00
AC:
0
AN:
19834
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19634
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30958
South Asian (SAS)
AF:
0.00
AC:
0
AN:
64736
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37198
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4412
European-Non Finnish (NFE)
AF:
0.00000192
AC:
2
AN:
1039698
Other (OTH)
AF:
0.00
AC:
0
AN:
53316
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
151940
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74214
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41432
American (AMR)
AF:
0.00
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5130
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10546
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67942
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
2
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T
Eigen
Benign
-0.031
Eigen_PC
Benign
0.085
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.51
T
M_CAP
Pathogenic
0.82
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
2.0
M
PhyloP100
0.74
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.35
Sift
Benign
0.12
T
Sift4G
Benign
0.14
T
Polyphen
0.099
B
Vest4
0.17
MutPred
0.37
Loss of solvent accessibility (P = 1e-04);
MVP
0.42
MPC
2.2
ClinPred
0.92
D
GERP RS
4.2
Varity_R
0.22
gMVP
0.64
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs12441516; hg19: chr15-43028683; API