Variant 12-48999125-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000421952.3(DDN):c.163A>T(p.Met55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DDN
ENST00000421952.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

DDN (HGNC:24458): (dendrin) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cell projection and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDN links:

DDN-AS1 (HGNC:53464): (DDN and PRKAG1 antisense RNA 1)

DDN-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDN	NM_015086.2 linkuse as main transcript	c.163A>T	p.Met55Leu	missense_variant	1/2	ENST00000421952.3	NP_055901.2
DDN-AS1	NR_147178.1 linkuse as main transcript	n.344+435T>A		intron_variant, non_coding_transcript_variant
DDN-AS1	NR_147179.1 linkuse as main transcript	n.344+435T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDN	ENST00000421952.3 linkuse as main transcript	c.163A>T	p.Met55Leu	missense_variant	1/2	1	NM_015086.2	ENSP00000390590	P1
DDN-AS1	ENST00000552933.2 linkuse as main transcript	n.324+435T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727230

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.:

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

Oct 06, 2021

The c.163A>T (p.M55L) alteration is located in exon 1 (coding exon 1) of the DDN gene. This alteration results from a A to T substitution at nucleotide position 163, causing the methionine (M) at amino acid position 55 to be replaced by a leucine (L). 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

0.25

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.31

Eigen

Benign

0.14

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.52

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.64

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Benign

0.47

Polyphen

0.80

Vest4

0.53

MutPred

0.26

Loss of MoRF binding (P = 0.0796);

MVP

0.45

MPC

1.5

ClinPred

0.96

GERP RS

3.7

Varity_R

0.82

gMVP

0.066

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