Variant chr9-108952296-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003798.4(CTNNAL1):c.1748T>C(p.Ile583Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CTNNAL1
NM_003798.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

CTNNAL1 (HGNC:2512): (catenin alpha like 1) Predicted to enable actin filament binding activity and cadherin binding activity. Acts upstream of or within Rho protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CTNNAL1 links:

CTNNAL1 (HGNC:):

CTNNAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091410756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNAL1	NM_003798.4 linkuse as main transcript	c.1748T>C	p.Ile583Thr	missense_variant	14/19	ENST00000325551.9	NP_003789.1	Q9UBT7-1B3KMX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTNNAL1	ENST00000325551.9 linkuse as main transcript	c.1748T>C	p.Ile583Thr	missense_variant	14/19	1	NM_003798.4	ENSP00000320434.4	Q9UBT7-1
CTNNAL1	ENST00000374595.8 linkuse as main transcript	c.1748T>C	p.Ile583Thr	missense_variant	14/19	1		ENSP00000363723.4	Q9UBT7-2
CTNNAL1	ENST00000374594.1 linkuse as main transcript	c.-50T>C		5_prime_UTR_premature_start_codon_gain_variant	3/8	3		ENSP00000363722.1	Q5JTQ9
CTNNAL1	ENST00000374594.1 linkuse as main transcript	c.-50T>C		5_prime_UTR_variant	3/8	3		ENSP00000363722.1	Q5JTQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251406

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727236

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:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 07, 2024

The c.1748T>C (p.I583T) alteration is located in exon 14 (coding exon 14) of the CTNNAL1 gene. This alteration results from a T to C substitution at nucleotide position 1748, causing the isoleucine (I) at amino acid position 583 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0095

.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.51

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.065

Sift

Benign

0.83

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0

B;B

Vest4

0.19

MutPred

0.62

Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);

MVP

0.37

MPC

0.16

ClinPred

0.39

GERP RS

3.6

Varity_R

0.038

gMVP

0.16

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