rs80338695

Positions:

• chr15-42730760-G-A

Variant summary

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

The NM_138477.4(CDAN1):​c.2012C>T​(p.Pro671Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 33)
• Consequence: CDAN1 NM_138477.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

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=0.30984572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDAN1	NM_138477.4	c.2012C>T	p.Pro671Leu	missense_variant	14/28	ENST00000356231.4	NP_612486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDAN1	ENST00000356231.4	c.2012C>T	p.Pro671Leu	missense_variant	14/28	1	NM_138477.4	ENSP00000348564.3
CDAN1	ENST00000562465.5	n.5C>T		non_coding_transcript_exon_variant	1/15	1		ENSP00000454246.1
CDAN1	ENST00000643434.1	n.*1190C>T		non_coding_transcript_exon_variant	12/25			ENSP00000494699.1
CDAN1	ENST00000643434.1	n.*1190C>T		3_prime_UTR_variant	12/25			ENSP00000494699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Benign	0.76
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.26	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.85	N
REVEL	Uncertain	0.39
Sift	Benign	0.69	T
Sift4G	Benign	1.0	T
Polyphen		0.024	B
Vest4		0.61
MutPred		0.30		Loss of catalytic residue at P671 (P = 0.0394);
MVP		0.73
MPC		0.46
ClinPred		0.50	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.37

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

Other links and lift over

dbSNP: rs80338695; hg19: chr15-43022958;