10-53940967-G-T

Position:

• chr10-53940967-G-T

Variant summary

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

The NM_001384140.1(PCDH15):​c.3131C>A​(p.Pro1044Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDH15 NM_001384140.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.3131C>A	p.Pro1044Gln	missense_variant	24/33	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.3131C>A	p.Pro1044Gln	missense_variant	24/38	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.3131C>A	p.Pro1044Gln	missense_variant	24/33	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.3131C>A	p.Pro1044Gln	missense_variant	24/38		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;.;.;.;.;T;T;T;T;.;.;T;.;T;.;.;.;.;.;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.42	.;.;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	.;.;.;.;.;.;.;D;.;D;D;.;D;.;.;D;D;D;.;D;D
REVEL	Benign	0.28
Sift	Benign	0.16	.;.;.;.;.;.;.;T;.;T;T;.;T;.;.;T;T;T;.;T;T
Sift4G	Uncertain	0.0020	D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.97, 1.0, 1.0, 1.0, 1.0	.;.;.;.;.;.;.;.;.;.;D;.;D;.;.;D;D;D;.;D;D
Vest4		0.70
MutPred		0.40		Loss of glycosylation at P1044 (P = 0.0227);Loss of glycosylation at P1044 (P = 0.0227);.;Loss of glycosylation at P1044 (P = 0.0227);Loss of glycosylation at P1044 (P = 0.0227);.;Loss of glycosylation at P1044 (P = 0.0227);.;.;.;Loss of glycosylation at P1044 (P = 0.0227);.;.;.;.;Loss of glycosylation at P1044 (P = 0.0227);Loss of glycosylation at P1044 (P = 0.0227);.;.;.;Loss of glycosylation at P1044 (P = 0.0227);
MVP		0.81
MPC		0.18
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-55700727;