10-27403350-A-G

Variant names:

• chr10-27403350-A-G
• rs2484180
• ENST00000642324.1:c.1219T>C

Variant summary

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

The ENST00000642324.1(PTCHD3):​c.1219T>C​(p.Cys407Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,612,416 control chromosomes in the GnomAD database, including 1,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.035 (229 hom., cov: 31)
  • Exomes 𝑓: 0.016 (891 hom.)
• Consequence: PTCHD3 ENST00000642324.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 28 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=0.002841711).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1219T>C	p.Cys407Arg	missense_variant	Exon 3 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1219T>C	p.Cys407Arg	missense_variant	Exon 3 of 4			ENSP00000495205.1

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5355 AN: 151858 Hom.: 228 Cov.: 31

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00996

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00674

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0315 AC: 7838 AN: 249072 AF XY: 0.0296

Gnomad AFR exome AF: 0.0782

Gnomad AMR exome AF: 0.00667

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.0525

Gnomad NFE exome AF: 0.00743

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0156 AC: 22755 AN: 1460440 Hom.: 891 Cov.: 36 AF XY: 0.0154 AC XY: 11218 AN XY: 726482

African (AFR) AF: 0.0772 AC: 2584 AN: 33464

American (AMR) AF: 0.00784 AC: 350 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00505 AC: 132 AN: 26120

East Asian (EAS) AF: 0.166 AC: 6574 AN: 39668

South Asian (SAS) AF: 0.0221 AC: 1898 AN: 86060

European-Finnish (FIN) AF: 0.0496 AC: 2632 AN: 53098

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5768

European-Non Finnish (NFE) AF: 0.00640 AC: 7113 AN: 1111286

Other (OTH) AF: 0.0237 AC: 1431 AN: 60350

GnomAD4 genome AF: 0.0353 AC: 5360 AN: 151976 Hom.: 229 Cov.: 31 AF XY: 0.0367 AC XY: 2726 AN XY: 74298

African (AFR) AF: 0.0745 AC: 3088 AN: 41424

American (AMR) AF: 0.00995 AC: 152 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.185 AC: 953 AN: 5162

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4814

European-Finnish (FIN) AF: 0.0489 AC: 517 AN: 10576

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00673 AC: 457 AN: 67944

Other (OTH) AF: 0.0214 AC: 45 AN: 2106

Alfa AF: 0.000355 Hom.: 40361

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00649 AC: 25

ExAC AF: 0.0316 AC: 3840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.46	N
MetaRNN	Benign	0.0028	T;T
MetaSVM	Uncertain	-0.092	T
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		2.0
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.1	D;.
REVEL	Uncertain	0.47
Sift	Benign	0.15	T;.
Sift4G	Uncertain	0.034	D;D
Polyphen		0.15	B;.
Vest4		0.36
MPC		0.31
ClinPred		0.047	T
GERP RS		2.9
Varity_R		0.46
Mutation Taster		=96/4	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: rs2484180; hg19: chr10-27692279; COSMIC: COSV107529119;