chr1-155718789-C-A

Variant names:

• chr1-155718789-C-A
• rs821551
• NM_004632.4:c.168+1661C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004632.4(DAP3):​c.168+1661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,628 control chromosomes in the GnomAD database, including 24,914 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (24914 hom., cov: 31)
• Consequence: DAP3 NM_004632.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• Publications: 23 publications found

Genes affected

DAP3 (HGNC:2673): (death associated protein 3) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that also participates in apoptotic pathways which are initiated by tumor necrosis factor-alpha, Fas ligand, and gamma interferon. This protein potentially binds ATP/GTP and might be a functional partner of the mitoribosomal protein S27. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. Pseudogenes corresponding to this gene are found on chromosomes 1q and 2q. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004632.4. 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
	DAP3	NM_004632.4	MANE Select	c.168+1661C>A		intron	N/A	NP_004623.1	P51398-1
	DAP3	NM_001199849.1		c.168+1661C>A		intron	N/A	NP_001186778.1	P51398-1
	DAP3	NM_033657.2		c.168+1661C>A		intron	N/A	NP_387506.1	P51398-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAP3	ENST00000368336.10	TSL:1 MANE Select	c.168+1661C>A		intron	N/A	ENSP00000357320.5	P51398-1
	DAP3	ENST00000343043.7	TSL:1	c.168+1661C>A		intron	N/A	ENSP00000341692.3	P51398-1
	DAP3	ENST00000878855.1		c.249+1661C>A		intron	N/A	ENSP00000548914.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79219 AN: 151514 Hom.: 24851 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79343 AN: 151628 Hom.: 24914 Cov.: 31 AF XY: 0.523 AC XY: 38691 AN XY: 74032

African (AFR) AF: 0.885 AC: 36589 AN: 41350

American (AMR) AF: 0.434 AC: 6590 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3466

East Asian (EAS) AF: 0.719 AC: 3709 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1984 AN: 4806

European-Finnish (FIN) AF: 0.418 AC: 4353 AN: 10404

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.349 AC: 23735 AN: 67932

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.441 Hom.: 2988

Bravo AF: 0.545

Asia WGS AF: 0.597 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.15
DANN	Benign	0.40
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs821551; hg19: chr1-155688580;