Variant 11-104037341-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001711.3(DDI1):c.519C>A(p.Ser173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

DDI1
NM_001001711.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.12

Variant links:

Genes affected

DDI1 (HGNC:18961): (DNA damage inducible 1 homolog 1) Predicted to enable aspartic-type endopeptidase activity. Involved in several processes, including cellular response to hydroxyurea; proteasomal protein catabolic process; and regulation of DNA stability. [provided by Alliance of Genome Resources, Apr 2022]

DDI1 links:

PDGFD (HGNC:30620): (platelet derived growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines, seven of which are found in this factor. This gene product only forms homodimers and, therefore, does not dimerize with the other three family members. It differs from alpha and beta members of this family in having an unusual N-terminal domain, the CUB domain. Two splice variants have been identified for this gene. [provided by RefSeq, Jul 2008]

PDGFD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.28405648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDI1	NM_001001711.3 linkuse as main transcript	c.519C>A	p.Ser173Arg	missense_variant	1/1	ENST00000302259.5	NP_001001711.1	Q8WTU0
PDGFD	NM_025208.5 linkuse as main transcript	c.125-37086G>T		intron_variant		ENST00000393158.7	NP_079484.1	Q9GZP0-1
PDGFD	NM_033135.4 linkuse as main transcript	c.125-37104G>T		intron_variant			NP_149126.1	Q9GZP0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDI1	ENST00000302259.5 linkuse as main transcript	c.519C>A	p.Ser173Arg	missense_variant	1/1	6	NM_001001711.3	ENSP00000302805.3	Q8WTU0
PDGFD	ENST00000393158.7 linkuse as main transcript	c.125-37086G>T		intron_variant		1	NM_025208.5	ENSP00000376865.2	Q9GZP0-1
PDGFD	ENST00000302251.9 linkuse as main transcript	c.125-37104G>T		intron_variant		1		ENSP00000302193.5	Q9GZP0-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152216

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74494

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 09, 2024

The c.519C>A (p.S173R) alteration is located in exon 1 (coding exon 1) of the DDI1 gene. This alteration results from a C to A substitution at nucleotide position 519, causing the serine (S) at amino acid position 173 to be replaced by an arginine (R). 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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

0.80

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.091

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.062

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.56

MutPred

0.43

Gain of helix (P = 0.0117);

MVP

0.23

MPC

0.83

ClinPred

0.98

GERP RS

-5.7

Varity_R

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over