rs2367202

Variant names:

• chr2-86118413-A-G
• rs2367202
• NM_017952.6:c.415-508A>G

Variant summary

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

The NM_017952.6(PTCD3):​c.415-508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,106 control chromosomes in the GnomAD database, including 45,216 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 0.76 (45216 hom., cov: 32)
• Consequence: PTCD3 NM_017952.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 8 publications found

Genes affected

PTCD3 (HGNC:24717): (pentatricopeptide repeat domain 3) Enables rRNA binding activity and ribosomal small subunit binding activity. Involved in mitochondrial translation. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in combined oxidative phosphorylation deficiency 51. [provided by Alliance of Genome Resources, Apr 2022]

PTCD3 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 51

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017952.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD3	NM_017952.6	MANE Select	c.415-508A>G		intron	N/A	NP_060422.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD3	ENST00000254630.12	TSL:1 MANE Select	c.415-508A>G		intron	N/A	ENSP00000254630.7
	PTCD3	ENST00000409783.6	TSL:5	c.414+1254A>G		intron	N/A	ENSP00000386922.3
	PTCD3	ENST00000465560.5	TSL:3	n.440-508A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115626 AN: 151988 Hom.: 45192 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.761 AC: 115704 AN: 152106 Hom.: 45216 Cov.: 32 AF XY: 0.763 AC XY: 56714 AN XY: 74356

African (AFR) AF: 0.573 AC: 23760 AN: 41462

American (AMR) AF: 0.807 AC: 12340 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3076 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3358 AN: 5158

South Asian (SAS) AF: 0.852 AC: 4112 AN: 4824

European-Finnish (FIN) AF: 0.848 AC: 8977 AN: 10588

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57470 AN: 68000

Other (OTH) AF: 0.792 AC: 1671 AN: 2110

Alfa AF: 0.817 Hom.: 162179

Bravo AF: 0.752

Asia WGS AF: 0.736 AC: 2560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.051
DANN	Benign	0.49
PhyloP100		-1.2
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: rs2367202; hg19: chr2-86345536;