NM_130848.3:c.374G>T

Variant names:

• chr5-135446735-C-A
• NM_130848.3:c.374G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130848.3(DCANP1):​c.374G>T​(p.Arg125Leu) 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. 13/20 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: 34)
• Consequence: DCANP1 NM_130848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057369977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCANP1	NM_130848.3	c.374G>T	p.Arg125Leu	missense_variant	Exon 1 of 1	ENST00000503143.3	NP_570900.1
TIFAB	NM_001099221.2	c.*2719G>T		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.374G>T	p.Arg125Leu	missense_variant	Exon 1 of 1	6	NM_130848.3	ENSP00000421871.1
TIFAB	ENST00000537858	c.*2719G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001099221.2	ENSP00000440509.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.18
DANN	Benign	0.74
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.015
Polyphen		0.33	B
Vest4		0.084
MutPred		0.21		Loss of phosphorylation at T123 (P = 0.0558);
MVP		0.085
MPC		0.025
ClinPred		0.10	T
GERP RS		-3.0
Varity_R		0.35
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-134782425;