chr15-36579919-C-G

Position:

• chr15-36579919-C-G

Variant summary

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

The NM_001321759.2(CDIN1):​c.59C>G​(p.Pro20Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDIN1 NM_001321759.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

Genes affected

CDIN1 (HGNC:26929): (CDAN1 interacting nuclease 1) This gene encodes a protein with two predicted helix-turn-helix domains. Mutations in this gene were found in families with congenital dyserythropoietic anemia type Ib. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

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=0.3862374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDIN1	NM_001321759.2	c.59C>G	p.Pro20Arg	missense_variant	1/11	ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6	c.59C>G	p.Pro20Arg	missense_variant	1/11	5	NM_001321759.2	ENSP00000455397	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital dyserythropoietic anemia type type 1B Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

SIB Swiss Institute of Bioinformatics

Jul 11, 2019

This variant is interpreted as a variant of uncertain significance for congenital dyserythropoietic anemia type Ib, autosomal recessive. The following ACMG Tag(s) were applied: PM2; PP3. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0079	T;.;.;.;T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.84	.;T;T;T;.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L;.;.;.;L;.;L
MutationTaster	Benign	0.99	D;D;D
PROVEAN	Benign	-0.51	N;.;N;N;.;.;N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D;.;D;T;.;.;D
Sift4G	Benign	0.28	T;.;D;T;.;.;T
Polyphen		1.0	D;.;.;.;D;.;D
Vest4		0.75
MutPred		0.25		Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);
MVP		0.65
MPC		0.26
ClinPred		0.87	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
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

LitVar

Other links and lift over

dbSNP: rs1595696464; hg19: chr15-36872120;