Genetic Variant ENST00000642324.1:c.1562T>C (chr10-27399036-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000642324.1(PTCHD3):c.1562T>C(p.Met521Thr) variant causes a missense change. The variant allele was found at a frequency of 0.656 in 1,611,132 control chromosomes in the GnomAD database, including 353,832 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29857 hom., cov: 30)

Exomes 𝑓: 0.66 ( 323975 hom. )

Consequence

PTCHD3
ENST00000642324.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

Publications

33 publications found

Variant links:

Genes affected

PTCHD3 (HGNC:24776): (patched domain containing 3 (gene/pseudogene)) Predicted to be located in sperm midpiece. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PTCHD3 links:

ENSG00000301548 (HGNC:):

ENSG00000301548 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000642324.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2129038E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642324.1. 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
	PTCHD3	NM_001034842.5		c.1562T>C	p.Met521Thr	missense	Exon 4 of 4	NP_001030014.2

Ensembl Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein
PTCHD3	ENST00000642324.1	c.1562T>C	p.Met521Thr	missense	Exon 4 of 4	ENSP00000495205.1
ENSG00000301548	ENST00000779634.1	n.85+27333A>G		intron	N/A
ENSG00000301548	ENST00000779635.1	n.86-19181A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94369

AN:

151808

Hom.:

29827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.643

GnomAD2 exomes

AF:

0.615

AC:

154447

AN:

251152

AF XY:

0.631

show subpopulations

Gnomad AFR exome

AF:

0.545

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.749

Gnomad EAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.659

AC:

962128

AN:

1459206

Hom.:

323975

Cov.:

AF XY:

0.663

AC XY:

481227

AN XY:

726034

show subpopulations

African (AFR)

AF:

0.545

AC:

18219

AN:

33438

American (AMR)

AF:

0.447

AC:

19999

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

19508

AN:

26114

East Asian (EAS)

AF:

0.275

AC:

10902

AN:

39678

South Asian (SAS)

AF:

0.697

AC:

60036

AN:

86192

European-Finnish (FIN)

AF:

0.682

AC:

36441

AN:

53412

Middle Eastern (MID)

AF:

0.739

AC:

4257

AN:

5762

European-Non Finnish (NFE)

AF:

0.679

AC:

753047

AN:

1109598

Other (OTH)

AF:

0.659

AC:

39719

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

16660

33320

49981

66641

83301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19150

38300

57450

76600

95750

<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:

0.622

AC:

94452

AN:

151926

Hom.:

29857

Cov.:

AF XY:

0.624

AC XY:

46316

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.549

AC:

22763

AN:

41444

American (AMR)

AF:

0.562

AC:

8567

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.749

AC:

2597

AN:

3466

East Asian (EAS)

AF:

0.343

AC:

1774

AN:

5174

South Asian (SAS)

AF:

0.665

AC:

3198

AN:

4812

European-Finnish (FIN)

AF:

0.687

AC:

7247

AN:

10542

Middle Eastern (MID)

AF:

0.705

AC:

206

AN:

292

European-Non Finnish (NFE)

AF:

0.678

AC:

46071

AN:

67928

Other (OTH)

AF:

0.639

AC:

1349

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.656

Hom.:

103876

Bravo

AF:

0.602

Asia WGS

AF:

0.506

AC:

1761

AN:

3478

EpiCase

AF:

0.691

EpiControl

AF:

0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.4

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.044

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.031

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.6

PhyloP100

4.0

PrimateAI

Benign

0.45

PROVEAN

Benign

3.1

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Varity_R

0.046

Mutation Taster

=88/12

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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