7-105994770-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152750.5(CDHR3):c.533C>A(p.Pro178Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.9e-7 (0 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056492656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.533C>A	p.Pro178Gln	missense_variant	5/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.269C>A	p.Pro90Gln	missense_variant	4/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.533C>A	p.Pro178Gln	missense_variant	5/19	1	NM_152750.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459734 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725894

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 11, 2021

The c.533C>A (p.P178Q) alteration is located in exon 5 (coding exon 5) of the CDHR3 gene. This alteration results from a C to A substitution at nucleotide position 533, causing the proline (P) at amino acid position 178 to be replaced by a glutamine (Q). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.87
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.058
Sift	Benign	0.51	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0010	B;.
Vest4		0.19
MutPred		0.38		Loss of glycosylation at P178 (P = 0.0579);.;
MVP		0.20
MPC		0.037
ClinPred		0.095	T
GERP RS		3.1
Varity_R		0.043
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105635216; COSMIC: COSV100488496;