rs587777100

Variant names:

• chr15-36697379-T-A
• rs587777100
• NM_001321759.2:c.533T>A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_001321759.2(CDIN1):​c.533T>A​(p.Leu178Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDIN1 NM_001321759.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 7.52
• Publications: 5 publications found

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]

CDIN1 Gene-Disease associations (from GenCC):

• congenital dyserythropoietic anemia type type 1B

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• congenital dyserythropoietic anemia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75
• PP5: Variant 15-36697379-T-A is Pathogenic according to our data. Variant chr15-36697379-T-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 97057.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321759.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	NM_001321759.2	MANE Select	c.533T>A	p.Leu178Gln	missense	Exon 8 of 11	NP_001308688.1	Q9Y2V0-1
	CDIN1	NM_001321761.2		c.533T>A	p.Leu178Gln	missense	Exon 8 of 11	NP_001308690.1	H3BS01
	CDIN1	NM_001290233.2		c.533T>A	p.Leu178Gln	missense	Exon 8 of 11	NP_001277162.1	A0A2R8YD89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIN1	ENST00000566621.6	TSL:5 MANE Select	c.533T>A	p.Leu178Gln	missense	Exon 8 of 11	ENSP00000455397.1	Q9Y2V0-1
	CDIN1	ENST00000437989.6	TSL:1	c.533T>A	p.Leu178Gln	missense	Exon 8 of 12	ENSP00000401362.2	Q9Y2V0-1
	CDIN1	ENST00000562877.5	TSL:1	c.239T>A	p.Leu80Gln	missense	Exon 8 of 11	ENSP00000457854.1	Q9Y2V0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Congenital dyserythropoietic anemia type type 1B (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.5
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.93	P
Vest4		0.98
MutPred		0.54		Gain of disorder (P = 0.0165)
MVP		0.62
MPC		0.50
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.81
gMVP		0.87
Mutation Taster		=1/99	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs587777100; hg19: chr15-36989580;