rs2241437

Positions:

• chr2-86133450-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017952.6(PTCD3):​c.1543+14T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,587,638 control chromosomes in the GnomAD database, including 2,173 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 0.035 (230 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1943 hom.)
• Consequence: PTCD3 NM_017952.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTCD3	NM_017952.6	c.1543+14T>G		intron_variant		ENST00000254630.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCD3	ENST00000254630.12	c.1543+14T>G		intron_variant		1	NM_017952.6	P1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5323 AN: 152232 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0468

GnomAD3 exomes AF: 0.0446 AC: 11199 AN: 251010 Hom.: 678 AF XY: 0.0439 AC XY: 5955 AN XY: 135684

Gnomad AFR exome AF: 0.00824

Gnomad AMR exome AF: 0.0244

Gnomad ASJ exome AF: 0.0187

Gnomad EAS exome AF: 0.234

Gnomad SAS exome AF: 0.0217

Gnomad FIN exome AF: 0.00801

Gnomad NFE exome AF: 0.0409

Gnomad OTH exome AF: 0.0404

GnomAD4 exome AF: 0.0400 AC: 57349 AN: 1435288 Hom.: 1943 Cov.: 30 AF XY: 0.0396 AC XY: 28324 AN XY: 715486

Gnomad4 AFR exome AF: 0.00723

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.0186

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.0226

Gnomad4 FIN exome AF: 0.00839

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0441

GnomAD4 genome AF: 0.0350 AC: 5334 AN: 152350 Hom.: 230 Cov.: 32 AF XY: 0.0350 AC XY: 2605 AN XY: 74500

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0333 Hom.: 38

Bravo AF: 0.0368

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2241437; hg19: chr2-86360573; COSMIC: COSV54479222; COSMIC: COSV54479222;