20-62890975-G-A

Position:

chr20-62890975-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001193369.2(DIDO1):c.3526C>T(p.Pro1176Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DIDO1
NM_001193369.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86

Variant links:

Genes affected

DIDO1 (HGNC:2680): (death inducer-obliterator 1) Apoptosis, a major form of cell death, is an efficient mechanism for eliminating unwanted cells and is of central importance for development and homeostasis in metazoan animals. In mice, the death inducer-obliterator-1 gene is upregulated by apoptotic signals and encodes a cytoplasmic protein that translocates to the nucleus upon apoptotic signal activation. When overexpressed, the mouse protein induced apoptosis in cell lines growing in vitro. This gene is similar to the mouse gene and therefore is thought to be involved in apoptosis. Alternatively spliced transcripts have been found for this gene, encoding multiple isoforms. [provided by RefSeq, Jul 2008]

DIDO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIDO1	NM_001193369.2 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/16	ENST00000395343.6	NP_001180298.1	Q9BTC0-4
DIDO1	NM_033081.3 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/16		NP_149072.2	Q9BTC0-4
DIDO1	NM_001193370.2 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/15		NP_001180299.1	Q9BTC0-1
DIDO1	NM_080797.4 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/15		NP_542987.2	Q9BTC0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIDO1	ENST00000395343.6 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/16	1	NM_001193369.2	ENSP00000378752.1	Q9BTC0-4
DIDO1	ENST00000395340.5 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/15	1		ENSP00000378749.1	Q9BTC0-1
DIDO1	ENST00000266070.8 linkuse as main transcript	c.3526C>T	p.Pro1176Ser	missense_variant	15/16	5		ENSP00000266070.4	Q9BTC0-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727198

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.3526C>T (p.P1176S) alteration is located in exon 15 (coding exon 13) of the DIDO1 gene. This alteration results from a C to T substitution at nucleotide position 3526, causing the proline (P) at amino acid position 1176 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.71

D;D;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.1

M;M;M

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-7.4

D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.12

T;T;D

Polyphen

0.99

D;D;D

Vest4

0.91

MutPred

0.47

Gain of phosphorylation at P1176 (P = 0.0524);Gain of phosphorylation at P1176 (P = 0.0524);Gain of phosphorylation at P1176 (P = 0.0524);

MVP

0.58

MPC

1.2

ClinPred

1.0

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over