3-41224535-T-C

Position:

• chr3-41224535-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1 PM2 BP6_Moderate

The NM_001330729.2(CTNNB1):​c.2T>C​(p.Met1?) variant causes a start lost 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNB1 NM_001330729.2 start_lost
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.02

Genes affected

CTNNB1 (HGNC:2514): (catenin beta 1) The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

CTNNB1 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-41224535-T-C is Benign according to our data. Variant chr3-41224535-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 562026.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNB1	NM_001904.4	c.23T>C	p.Met8Thr	missense_variant	3/15	ENST00000349496.11	NP_001895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNB1	ENST00000349496.11	c.23T>C	p.Met8Thr	missense_variant	3/15	1	NM_001904.4	ENSP00000344456.5
CTNNB1	ENST00000645982.1	c.23T>C	p.Met8Thr	missense_variant	3/16			ENSP00000494845.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;.;T;T;T;T;.;.;.;T;T;.;T;T;T;T;.;T;T;T;T;T;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	.;D;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;D;.;.;.;.;T;D;D;.;.;D;.;.;.;.;D;.;D;.;.;.;.;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.46	T;D;T;D;T;T;T;T;T;D;T;T;D;D;T;T;T;D;D;D;D;T;T;T;T;T;T;D;T;T;T;D;T;T;T;D;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;.;L;.;L;L;L;L;L;.;L;L;.;.;L;L;L;.;.;.;.;L;L;.;.;.;L;.;.;L;L;.;L;.;L;.;L;L;L;L;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.7	.;N;.;.;N;.;D;.;N;.;N;N;.;.;N;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	.;D;.;.;D;.;.;.;D;.;D;D;.;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
Sift4G	Pathogenic	0.0	.;D;.;.;D;.;.;.;D;.;D;D;.;.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;D
Polyphen		0.12	B;.;B;.;B;B;B;B;B;.;B;B;.;.;B;B;B;.;.;.;.;B;B;.;.;.;B;.;.;B;B;.;B;.;B;.;B;B;B;B;B
Vest4		0.76, 0.77, 0.76, 0.78, 0.92
MutPred		0.23		Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;.;.;.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);.;Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);
MVP		0.93
MPC		1.3
ClinPred		0.76	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.65

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: chr3-41266026;