chr2-86106252-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017952.6(PTCD3):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00751 in 1,613,754 control chromosomes in the GnomAD database, including 792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 428 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 364 hom. )

Consequence

PTCD3
NM_017952.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.99

Publications

6 publications found

Variant links:

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 links:

POLR1A (HGNC:17264): (RNA polymerase I subunit A) The protein encoded by this gene is the largest subunit of the RNA polymerase I complex. The encoded protein represents the catalytic subunit of the complex, which transcribes DNA into ribosomal RNA precursors. Defects in this gene are a cause of the Cincinnati type of acrofacial dysostosis. [provided by RefSeq, May 2016]

POLR1A Gene-Disease associations (from GenCC):

acrofacial dysostosis Cincinnati type
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
leukodystrophy, hypomyelinating, 27
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

POLR1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027564764).

BP6

Variant 2-86106252-C-T is Benign according to our data. Variant chr2-86106252-C-T is described in ClinVar as Benign. ClinVar VariationId is 1273760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD3	NM_017952.6	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 24	NP_060422.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCD3	ENST00000254630.12	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 24	ENSP00000254630.7	Q96EY7-1
PTCD3	ENST00000898160.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 24	ENSP00000568219.1
PTCD3	ENST00000898158.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 24	ENSP00000568217.1

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6045

AN:

152166

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.0104

AC:

2605

AN:

251368

AF XY:

0.00766

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.00723

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00416

AC:

6075

AN:

1461470

Hom.:

364

Cov.:

AF XY:

0.00363

AC XY:

2636

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.140

AC:

4677

AN:

33442

American (AMR)

AF:

0.00830

AC:

371

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.000522

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00781

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000358

AC:

398

AN:

1111796

Other (OTH)

AF:

0.00889

AC:

537

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

274

549

823

1098

1372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0397

AC:

6045

AN:

152284

Hom.:

428

Cov.:

AF XY:

0.0381

AC XY:

2838

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.138

AC:

5748

AN:

41532

American (AMR)

AF:

0.0135

AC:

207

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68028

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

261

522

784

1045

1306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0173

Hom.:

376

Bravo

AF:

0.0451

ESP6500AA

AF:

0.131

AC:

576

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0128

AC:

1557

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0076

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

4.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.43

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.51

MPC

0.31

ClinPred

0.062

GERP RS

5.2

PromoterAI

-0.49

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.27

gMVP

0.68

Mutation Taster

=76/24

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over