chr5-135446646-G-T

Variant names:

• chr5-135446646-G-T
• rs761040438
• NM_130848.3:c.463C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130848.3(DCANP1):​c.463C>A​(p.Leu155Met) 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 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L155V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCANP1 NM_130848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13037297).

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.463C>A	p.Leu155Met	missense	Exon 1 of 1	NP_570900.1	Q8TF63
	TIFAB	NM_001099221.2	MANE Select	c.*2808C>A		3_prime_UTR	Exon 2 of 2	NP_001092691.1	Q6ZNK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCANP1	ENST00000503143.3	TSL:6 MANE Select	c.463C>A	p.Leu155Met	missense	Exon 1 of 1	ENSP00000421871.1	Q8TF63
	TIFAB	ENST00000537858.2	TSL:1 MANE Select	c.*2808C>A		3_prime_UTR	Exon 2 of 2	ENSP00000440509.1	Q6ZNK6
	ENSG00000249639	ENST00000732724.1		n.118+503G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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: 53400

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.20
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.9
DANN	Benign	0.82
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.17
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Polyphen		1.0	D
Vest4		0.23
MutPred		0.24		Gain of ubiquitination at K160 (P = 0.102)
MVP		0.17
MPC		0.057
ClinPred		0.18	T
GERP RS		1.3
Varity_R		0.34
gMVP		0.0014
Mutation Taster		=100/0	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: rs761040438; hg19: chr5-134782336;