11-57795622-C-T

Variant summary

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

The NM_001085458.2(CTNND1):c.313C>T(p.Pro105Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTNND1 NM_001085458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

TMX2-CTNND1 (HGNC:):

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	UniProt
CTNND1	NM_001085458.2	c.313C>T	p.Pro105Ser	missense_variant	5/21	ENST00000399050.10
TMX2-CTNND1	NR_037646.1	n.872C>T		non_coding_transcript_exon_variant	6/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND1	ENST00000399050.10	c.313C>T	p.Pro105Ser	missense_variant	5/21	1	NM_001085458.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
Cadd	Uncertain	25
Dann	Pathogenic	1.0
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.54	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	0.34	D
MutationAssessor	Uncertain	2.1	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	Uncertain	0.72	T
PROVEAN	Benign	-2.2	N;N;N;D;D;N;N;N;D;D;N;D;D;D;D;N;D;D;D;D;D;D;D;D;N;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.083	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;T
Sift4G	Benign	0.24	T;T;T;T;D;T;T;T;D;D;T;D;T;T;T;T;D;T;T;T;D;D;D;T;T;D;D
Polyphen		0.64	P;P;D;.;.;D;.;D;.;.;P;.;.;.;.;P;.;D;.;D;.;.;.;.;.;.;.
Vest4		0.73
MutPred		0.29		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);.;.;.;.;Loss of loop (P = 0.0203);.;.;.;.;.;.;.;.;Loss of loop (P = 0.0203);.;.;
MVP		0.76
MPC		1.1
ClinPred		0.82	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.61

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: chr11-57563094;