chr20-62890996-G-A

Position:

chr20-62890996-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001193369.2(DIDO1):c.3505C>T(p.Pro1169Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

DIDO1
NM_001193369.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3087039).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DIDO1	NM_001193369.2 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/16	ENST00000395343.6	NP_001180298.1
DIDO1	NM_033081.3 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/16		NP_149072.2
DIDO1	NM_001193370.2 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/15		NP_001180299.1
DIDO1	NM_080797.4 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/15		NP_542987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIDO1	ENST00000395343.6 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/16	1	NM_001193369.2	ENSP00000378752	P2	Q9BTC0-4
DIDO1	ENST00000395340.5 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/15	1		ENSP00000378749	A2	Q9BTC0-1
DIDO1	ENST00000266070.8 linkuse as main transcript	c.3505C>T	p.Pro1169Ser	missense_variant	15/16	5		ENSP00000266070	P2	Q9BTC0-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251450

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000824

AC:

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

Mar 18, 2024

The c.3505C>T (p.P1169S) 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 3505, causing the proline (P) at amino acid position 1169 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

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.58

D;D;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.060

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.54

MutPred

0.27

Gain of phosphorylation at P1169 (P = 0.0658);Gain of phosphorylation at P1169 (P = 0.0658);Gain of phosphorylation at P1169 (P = 0.0658);

MVP

0.46

MPC

1.2

ClinPred

0.96

GERP RS

4.3

Varity_R

0.15

gMVP

0.36

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