15-42736485-C-G

Variant names:

• chr15-42736485-C-G
• NM_138477.4:c.386G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138477.4(CDAN1):​c.386G>C​(p.Arg129Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000772 in 1,295,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CDAN1 NM_138477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39364713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.386G>C	p.Arg129Pro	missense_variant	Exon 2 of 28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.386G>C	p.Arg129Pro	missense_variant	Exon 2 of 28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000643434.1	n.91-404G>C		intron_variant	Intron 1 of 24			ENSP00000494699.1
CDAN1	ENST00000563260.1	c.*77G>C		downstream_gene_variant		3		ENSP00000455536.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.72e-7 AC: 1 AN: 1295712 Hom.: 0 Cov.: 33 AF XY: 0.00000157 AC XY: 1 AN XY: 636472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.62e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.19	N
REVEL	Uncertain	0.32
Sift	Benign	0.068	T
Sift4G	Benign	0.40	T
Polyphen		0.99	D
Vest4		0.26
MutPred		0.35		Loss of solvent accessibility (P = 0.0015);
MVP		0.34
MPC		2.3
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.25
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-43028683;