2-86123541-A-G

Position:

• chr2-86123541-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCD3	NM_017952.6	c.655-160A>G		intron_variant		ENST00000254630.12	NP_060422.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCD3	ENST00000254630.12	c.655-160A>G		intron_variant		1	NM_017952.6	ENSP00000254630	P1
PTCD3	ENST00000409783.6	c.531-160A>G		intron_variant		5		ENSP00000386922
PTCD3	ENST00000480102.1	n.102-160A>G		intron_variant, non_coding_transcript_variant		4
PTCD3	ENST00000484203.5	n.131-160A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.715

Alfa AF: 0.798 Hom.: 35265

Bravo AF: 0.624

Asia WGS AF: 0.694 AC: 2412 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	1.5
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1025104; hg19: chr2-86350664; COSMIC: COSV54477917; COSMIC: COSV54477917;