7-106001584-T-C

Variant summary

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

The NM_152750.5(CDHR3):c.836T>C(p.Val279Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.301

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=0.031498164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.836T>C	p.Val279Ala	missense_variant	7/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.572T>C	p.Val191Ala	missense_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.836T>C	p.Val279Ala	missense_variant	7/19	1	NM_152750.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 29, 2023

The c.836T>C (p.V279A) alteration is located in exon 7 (coding exon 7) of the CDHR3 gene. This alteration results from a T to C substitution at nucleotide position 836, causing the valine (V) at amino acid position 279 to be replaced by an alanine (A). 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	0.063
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	3.3
Dann	Benign	0.70
DEOGEN2	Benign	0.0010	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.031	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.62	N;N;N
REVEL	Benign	0.052
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.090
MutPred		0.49		Loss of ubiquitination at K281 (P = 0.0896);.;.;
MVP		0.040
MPC		0.039
ClinPred		0.022	T
GERP RS		-5.0
Varity_R		0.023
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: chr7-105642030;