Genetic Variant DCANP1:p.Ala104Glu (chr5-135446798-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130848.3(DCANP1):c.311C>A(p.Ala104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DCANP1
NM_130848.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.820

Publications

2 publications found

Variant links:

Genes affected

DCANP1 (HGNC:24459): (dendritic cell associated nuclear protein 1) This intronless gene is specifically expressed in dendritic cells (DCs), which are potent antigen-presenting cells involved in activating naive T cells to initiate antigen-specific immune response. The encoded protein is localized mainly in the perinucleus. One of the alleles (A/T) of this gene, that causes premature translation termination at aa 117, has been associated with an increased prevalence of major depression in humans. [provided by RefSeq, Jul 2008]

DCANP1 links:

TIFAB (HGNC:34024): (TIFA inhibitor) Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

TIFAB links:

ENSG00000249639 (HGNC:):

ENSG00000249639 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06487742).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130848.3. 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
	DCANP1	NM_130848.3	MANE Select	c.311C>A	p.Ala104Glu	missense	Exon 1 of 1	NP_570900.1	Q8TF63
	TIFAB	NM_001099221.2	MANE Select	c.*2656C>A		3_prime_UTR	Exon 2 of 2	NP_001092691.1	Q6ZNK6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCANP1	ENST00000503143.3	TSL:6 MANE Select	c.311C>A	p.Ala104Glu	missense	Exon 1 of 1	ENSP00000421871.1	Q8TF63
TIFAB	ENST00000537858.2	TSL:1 MANE Select	c.*2656C>A		3_prime_UTR	Exon 2 of 2	ENSP00000440509.1	Q6ZNK6
ENSG00000249639	ENST00000732724.1		n.118+655G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251130

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111812

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.23

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.044

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.23

M_CAP

Benign

0.0088

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.82

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.16

Polyphen

0.74

Vest4

0.12

MutPred

0.059

Gain of solvent accessibility (P = 0.0456)

MVP

0.030

MPC

0.061

ClinPred

0.25

GERP RS

-6.4

Varity_R

0.41

gMVP

0.010

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over