Genetic Variant DCANP1:p.His236Tyr (chr5-135446403-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_130848.3(DCANP1):c.706C>T(p.His236Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,608,448 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

DCANP1
NM_130848.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.156

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022703916).

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.706C>T	p.His236Tyr	missense	Exon 1 of 1	NP_570900.1	Q8TF63
	TIFAB	NM_001099221.2	MANE Select	c.*3051C>T		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.706C>T	p.His236Tyr	missense	Exon 1 of 1	ENSP00000421871.1	Q8TF63
TIFAB	ENST00000537858.2	TSL:1 MANE Select	c.*3051C>T		3_prime_UTR	Exon 2 of 2	ENSP00000440509.1	Q6ZNK6
ENSG00000249639	ENST00000732724.1		n.118+260G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

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:

0.0000800

AC:

AN:

250148

AF XY:

0.0000888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1456120

Hom.:

Cov.:

AF XY:

0.0000373

AC XY:

AN XY:

723070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.00

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00111

AC:

AN:

39484

South Asian (SAS)

AF:

0.00

AC:

AN:

86016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107480

Other (OTH)

AF:

0.0000166

AC:

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.0000263

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.050

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.34

M_CAP

Benign

0.0072

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.16

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.13

Polyphen

0.84

Vest4

0.13

MutPred

0.064

Gain of phosphorylation at H236 (P = 0.0489)

MVP

0.22

MPC

0.019

ClinPred

0.17

GERP RS

0.30

Varity_R

0.41

gMVP

0.00060

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over