NM_015086.2:c.142C>T

Variant names:

• chr12-48999146-G-A
• rs1428874326
• NM_015086.2:c.142C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015086.2(DDN):​c.142C>T​(p.Arg48Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: DDN NM_015086.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.174
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07481119).
• BS2: High AC in GnomAd4 at 71 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015086.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDN	NM_015086.2	MANE Select	c.142C>T	p.Arg48Cys	missense	Exon 1 of 2	NP_055901.2	O94850
	DDN-AS1	NR_147178.1		n.344+456G>A		intron	N/A
	DDN-AS1	NR_147179.1		n.344+456G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDN	ENST00000421952.3	TSL:1 MANE Select	c.142C>T	p.Arg48Cys	missense	Exon 1 of 2	ENSP00000390590.2	O94850
	DDN-AS1	ENST00000547395.1	TSL:2	n.293+456G>A		intron	N/A
	DDN-AS1	ENST00000547866.1	TSL:3	n.319+456G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

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

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251110 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.000467 AC: 71 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.000727 AC XY: 54 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00465 AC: 71 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000502

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.17
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.23
Sift	Benign	0.067	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.29
MutPred		0.43		Gain of catalytic residue at Y45 (P = 0.0065)
MVP		0.48
MPC		0.89
ClinPred		0.29	T
GERP RS		3.7
PromoterAI		-0.20	Neutral
Varity_R		0.16
gMVP		0.12
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1428874326; hg19: chr12-49392929;