chr10-27399036-A-T

Variant names:

• chr10-27399036-A-T
• rs2505327
• ENST00000642324.1:c.1562T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034842.5(PTCHD3):​c.1562T>A​(p.Met521Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTCHD3 NM_001034842.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 33 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20896652).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034842.5. 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>A	p.Met521Lys	missense	Exon 4 of 4	NP_001030014.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCHD3	ENST00000642324.1		c.1562T>A	p.Met521Lys	missense	Exon 4 of 4	ENSP00000495205.1
	ENSG00000301548	ENST00000779634.1		n.85+27333A>T		intron	N/A
	ENSG00000301548	ENST00000779635.1		n.86-19181A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460712 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 726736

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110944

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 103876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.036	B
Vest4		0.38
MutPred		0.65		Gain of catalytic residue at M521 (P = 0.0014)
MVP		0.12
MPC		0.16
ClinPred		0.28	T
GERP RS		4.1
Varity_R		0.60
Mutation Taster		=86/14	polymorphism

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: rs2505327; hg19: chr10-27687965;