10-27403350-A-G

Position:

• chr10-27403350-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034842.5(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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C407G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.035 (229 hom., cov: 31)
  • Exomes 𝑓: 0.016 (891 hom.)
• Consequence: PTCHD3 NM_001034842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1219T>C	p.Cys407Arg	missense_variant	3/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1219T>C	p.Cys407Arg	missense_variant	3/4			ENSP00000495205	P1

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

GnomAD3 exomes AF: 0.0315 AC: 7838 AN: 249072 Hom.: 434 AF XY: 0.0296 AC XY: 3994 AN XY: 134732

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 SAS exome AF: 0.0218

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

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.00784

Gnomad4 ASJ exome AF: 0.00505

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.00640

Gnomad4 OTH exome AF: 0.0237

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

Gnomad4 AFR AF: 0.0745

Gnomad4 AMR AF: 0.00995

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.00673

Gnomad4 OTH AF: 0.0214

Alfa AF: 0.000498 Hom.: 27715

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;.
MutationTaster	Benign	0.13	P
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

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

LitVar

Other links and lift over

dbSNP: rs2484180; hg19: chr10-27692279;