rs821551

Positions:

• chr1-155718789-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAP3	NM_004632.4	c.168+1661C>A		intron_variant		ENST00000368336.10	NP_004623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAP3	ENST00000368336.10	c.168+1661C>A		intron_variant		1	NM_004632.4	ENSP00000357320	P1

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

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.466

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.15
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs821551; hg19: chr1-155688580;