5-135446760-T-C

Variant names:

• chr5-135446760-T-C
• rs12520799
• NM_130848.3:c.349A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130848.3(DCANP1):​c.349A>G​(p.Arg117Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCANP1 NM_130848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 44 publications found

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]

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]

ENSG00000249639 (HGNC:):

ACMG classification

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=0.030736744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCANP1	NM_130848.3	c.349A>G	p.Arg117Gly	missense_variant	Exon 1 of 1	ENST00000503143.3	NP_570900.1
TIFAB	NM_001099221.2	c.*2694A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000537858.2	NP_001092691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCANP1	ENST00000503143.3	c.349A>G	p.Arg117Gly	missense_variant	Exon 1 of 1	6	NM_130848.3	ENSP00000421871.1
TIFAB	ENST00000537858.2	c.*2694A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001099221.2	ENSP00000440509.1
ENSG00000249639	ENST00000732724.1	n.118+617T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14077

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.6
DANN	Benign	0.71
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.21
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.054
Polyphen		0.0	B
Vest4		0.13
MutPred		0.16		Loss of stability (P = 0.0148);
MVP		0.19
MPC		0.012
ClinPred		0.022	T
GERP RS		-5.9
Varity_R		0.12
gMVP		0.011
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12520799; hg19: chr5-134782450;