Variant 11-57795716-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001085458.2(CTNND1):c.407G>A(p.Arg136His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,444,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R136C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CTNND1
NM_001085458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

CTNND1 (HGNC:2515): (catenin delta 1) This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

CTNND1 links:

TMX2-CTNND1 (HGNC:):

TMX2-CTNND1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND1	NM_001085458.2 linkuse as main transcript	c.407G>A	p.Arg136His	missense_variant	5/21	ENST00000399050.10
TMX2-CTNND1	NR_037646.1 linkuse as main transcript	n.966G>A		non_coding_transcript_exon_variant	6/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND1	ENST00000399050.10 linkuse as main transcript	c.407G>A	p.Arg136His	missense_variant	5/21	1	NM_001085458.2		O60716-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1444898

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

718452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.0000503

Gnomad4 ASJ exome

AF:

0.0000394

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.407G>A (p.R136H) alteration is located in exon 5 (coding exon 3) of the CTNND1 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a histidine (H). 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

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

.;T;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

.;D;D;.;.;D;D;D;.;.;.;D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.65

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.42

MutationAssessor

Uncertain

2.3

M;.;M;.;.;M;M;M;.;.;M;.;.;.;.;M;.;.;.;.;.;.;.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;D;D;T;T;T;D;D;T;D;D;D;D;T;D;D;D;D;D;D;D;D;T;D;D

Polyphen

1.0

D;D;D;.;.;D;.;D;.;.;D;.;.;.;.;D;.;D;.;D;.;.;.;.;.;.;.

Vest4

0.71

MutPred

0.45

Loss of MoRF binding (P = 0.0371);Loss of MoRF binding (P = 0.0371);Loss of MoRF binding (P = 0.0371);.;.;Loss of MoRF binding (P = 0.0371);Loss of MoRF binding (P = 0.0371);Loss of MoRF binding (P = 0.0371);.;.;Loss of MoRF binding (P = 0.0371);.;.;.;.;Loss of MoRF binding (P = 0.0371);.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0371);.;.;

MVP

0.88

MPC

1.2

ClinPred

0.61

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.60

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

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