rs1075622

Variant names:

• chr2-86110807-T-C
• rs1075622
• NM_017952.6:c.195-306T>C

Variant summary

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

The NM_017952.6(PTCD3):​c.195-306T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,074 control chromosomes in the GnomAD database, including 42,248 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 0.72 (42248 hom., cov: 32)
• Consequence: PTCD3 NM_017952.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 11 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 = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCD3	NM_017952.6	c.195-306T>C		intron_variant	Intron 3 of 23	ENST00000254630.12	NP_060422.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCD3	ENST00000254630.12	c.195-306T>C		intron_variant	Intron 3 of 23	1	NM_017952.6	ENSP00000254630.7

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110044 AN: 151956 Hom.: 42245 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.724 AC: 110087 AN: 152074 Hom.: 42248 Cov.: 32 AF XY: 0.726 AC XY: 54015 AN XY: 74350

African (AFR) AF: 0.445 AC: 18443 AN: 41414

American (AMR) AF: 0.792 AC: 12104 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3073 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3377 AN: 5176

South Asian (SAS) AF: 0.821 AC: 3963 AN: 4828

European-Finnish (FIN) AF: 0.849 AC: 8979 AN: 10576

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57581 AN: 68012

Other (OTH) AF: 0.773 AC: 1629 AN: 2108

Alfa AF: 0.801 Hom.: 110689

Bravo AF: 0.710

Asia WGS AF: 0.715 AC: 2486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.12
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: rs1075622; hg19: chr2-86337930; COSMIC: COSV54481826; COSMIC: COSV54481826;