chr2-86123541-A-G

Variant names:

• chr2-86123541-A-G
• rs1025104
• NM_017952.6:c.655-160A>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.655-160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,142 control chromosomes in the GnomAD database, including 38,221 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 0.65 (38221 hom., cov: 32)
• Consequence: PTCD3 NM_017952.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 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.655-160A>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.655-160A>G		intron	N/A	ENSP00000254630.7
	PTCD3	ENST00000409783.6	TSL:5	c.531-160A>G		intron	N/A	ENSP00000386922.3
	PTCD3	ENST00000480102.1	TSL:4	n.102-160A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98763 AN: 152024 Hom.: 38229 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.649 AC: 98766 AN: 152142 Hom.: 38221 Cov.: 32 AF XY: 0.654 AC XY: 48666 AN XY: 74398

African (AFR) AF: 0.194 AC: 8067 AN: 41496

American (AMR) AF: 0.761 AC: 11622 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3013 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3366 AN: 5168

South Asian (SAS) AF: 0.819 AC: 3951 AN: 4824

European-Finnish (FIN) AF: 0.848 AC: 8964 AN: 10576

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57334 AN: 68006

Other (OTH) AF: 0.715 AC: 1512 AN: 2114

Alfa AF: 0.790 Hom.: 41187

Bravo AF: 0.624

Asia WGS AF: 0.694 AC: 2412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1025104; hg19: chr2-86350664; COSMIC: COSV54477917; COSMIC: COSV54477917;