ENST00000642324.1:c.1418A>G

Variant names:

• chr10-27399180-T-C
• rs2429485
• ENST00000642324.1:c.1418A>G

Variant summary

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

The ENST00000642324.1(PTCHD3):​c.1418A>G​(p.Asp473Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,603,836 control chromosomes in the GnomAD database, including 352,143 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 (29328 hom., cov: 25)
  • Exomes 𝑓: 0.66 (322815 hom.)
• Consequence: PTCHD3 ENST00000642324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 29 publications found

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]

ENSG00000301548 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=4.6696587E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1418A>G	p.Asp473Gly	missense_variant	Exon 4 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1418A>G	p.Asp473Gly	missense_variant	Exon 4 of 4			ENSP00000495205.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 92951 AN: 149754 Hom.: 29303 Cov.: 25

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.641

GnomAD2 exomes AF: 0.613 AC: 150155 AN: 244942 AF XY: 0.630

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.659 AC: 958583 AN: 1453974 Hom.: 322815 Cov.: 43 AF XY: 0.663 AC XY: 479703 AN XY: 723742

African (AFR) AF: 0.545 AC: 18224 AN: 33446

American (AMR) AF: 0.447 AC: 20001 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 19507 AN: 26114

East Asian (EAS) AF: 0.275 AC: 10908 AN: 39690

South Asian (SAS) AF: 0.697 AC: 60053 AN: 86196

European-Finnish (FIN) AF: 0.680 AC: 32429 AN: 47668

Middle Eastern (MID) AF: 0.739 AC: 4259 AN: 5766

European-Non Finnish (NFE) AF: 0.679 AC: 753483 AN: 1110074

Other (OTH) AF: 0.659 AC: 39719 AN: 60302

GnomAD4 genome AF: 0.621 AC: 93024 AN: 149862 Hom.: 29328 Cov.: 25 AF XY: 0.622 AC XY: 45473 AN XY: 73056

African (AFR) AF: 0.547 AC: 22287 AN: 40746

American (AMR) AF: 0.561 AC: 8426 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2582 AN: 3450

East Asian (EAS) AF: 0.343 AC: 1748 AN: 5102

South Asian (SAS) AF: 0.663 AC: 3126 AN: 4714

European-Finnish (FIN) AF: 0.685 AC: 6902 AN: 10082

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.678 AC: 45744 AN: 67474

Other (OTH) AF: 0.637 AC: 1326 AN: 2080

Alfa AF: 0.653 Hom.: 107106

Bravo AF: 0.602

TwinsUK AF: 0.682 AC: 2529

ALSPAC AF: 0.680 AC: 2620

ESP6500AA AF: 0.534 AC: 2355

ESP6500EA AF: 0.681 AC: 5856

ExAC AF: 0.618 AC: 75049

Asia WGS AF: 0.505 AC: 1759 AN: 3478

EpiCase AF: 0.691

EpiControl AF: 0.695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.24
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.071	N
MetaRNN	Benign	0.0000047	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L;.
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.17
Sift	Benign	0.41	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.0010	B;.
Vest4		0.15
MPC		0.13
ClinPred		0.014	T
GERP RS		-0.12
Varity_R		0.11
Mutation Taster		=97/3	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: rs2429485; hg19: chr10-27688109; COSMIC: COSV71256303;