chr10-27403241-A-G

Position:

• chr10-27403241-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034842.5(PTCHD3):​c.1328T>C​(p.Ile443Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTCHD3 NM_001034842.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15771559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.1328T>C	p.Ile443Thr	missense_variant	3/4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.1328T>C	p.Ile443Thr	missense_variant	3/4			ENSP00000495205	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461786 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.1328T>C (p.I443T) alteration is located in exon 3 (coding exon 3) of the PTCHD3 gene. This alteration results from a T to C substitution at nucleotide position 1328, causing the isoleucine (I) at amino acid position 443 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	0.95	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.45	N;.
REVEL	Benign	0.26
Sift	Benign	0.72	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.12	B;.
Vest4		0.19
MutPred		0.65		Gain of glycosylation at I443 (P = 0.0265);Gain of glycosylation at I443 (P = 0.0265);
MVP		0.26
MPC		0.13
ClinPred		0.43	T
GERP RS		1.6
Varity_R		0.10

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: rs910134524; hg19: chr10-27692170;