Variant chr7-105980998-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152750.5(CDHR3):c.280T>G(p.Phe94Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,457,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CDHR3
NM_152750.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Variant links:

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]

CDHR3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27518374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR3	NM_152750.5 linkuse as main transcript	c.280T>G	p.Phe94Val	missense_variant	3/19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2 linkuse as main transcript	c.16T>G	p.Phe6Val	missense_variant	2/18		NP_001288090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14 linkuse as main transcript	c.280T>G	p.Phe94Val	missense_variant	3/19	1	NM_152750.5	ENSP00000325954	P1	Q6ZTQ4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242170

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457680

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724610

show subpopulations

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:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.280T>G (p.F94V) alteration is located in exon 3 (coding exon 3) of the CDHR3 gene. This alteration results from a T to G substitution at nucleotide position 280, causing the phenylalanine (F) at amino acid position 94 to be replaced by a valine (V). 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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.18

Sift

Uncertain

0.029

D;T

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;.

Vest4

0.32

MutPred

0.46

Gain of disorder (P = 0.1506);.;

MVP

0.60

MPC

0.29

ClinPred

0.96

GERP RS

5.0

Varity_R

0.67

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over