15-36645281-A-G

Position:

• chr15-36645281-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001321759.2(CDIN1):​c.206A>G​(p.Tyr69Cys) variant causes a missense change. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDIN1 NM_001321759.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.14

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDIN1	NM_001321759.2	c.206A>G	p.Tyr69Cys	missense_variant	3/11	ENST00000566621.6	NP_001308688.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDIN1	ENST00000566621.6	c.206A>G	p.Tyr69Cys	missense_variant	3/11	5	NM_001321759.2	ENSP00000455397	P1
	ENST00000565366.1	n.122-3321T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690594

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.;T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;.;D;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PROVEAN	Pathogenic	-4.6	D;.;D;.;.;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;.;D;.;.;D
Sift4G	Uncertain	0.016	D;.;D;.;.;D
Polyphen		1.0	D;.;.;D;.;D
Vest4		0.87
MutPred		0.67		Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);Loss of disorder (P = 0.0834);
MVP		0.48
MPC		0.68
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.31
gMVP		0.69

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: chr15-36937482;