Variant 9-108972751-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003798.4(CTNNAL1):c.1271C>G(p.Thr424Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00521 in 1,563,000 control chromosomes in the GnomAD database, including 396 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.028 ( 194 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 202 hom. )

Consequence

CTNNAL1
NM_003798.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.64

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014653206).

BP6

Variant 9-108972751-G-C is Benign according to our data. Variant chr9-108972751-G-C is described in ClinVar as [Benign]. Clinvar id is 776438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNAL1	NM_003798.4 linkuse as main transcript	c.1271C>G	p.Thr424Ser	missense_variant	9/19	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.1271C>G	p.Thr424Ser	missense_variant	9/19	1	NM_003798.4	ENSP00000320434.4	Q9UBT7-1
CTNNAL1	ENST00000374595.8 linkuse as main transcript	c.1271C>G	p.Thr424Ser	missense_variant	9/19	1		ENSP00000363723.4	Q9UBT7-2
CTNNAL1	ENST00000488130.1 linkuse as main transcript	n.542C>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4136

AN:

145696

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0996

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00801

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00703

AC:

1766

AN:

251200

Hom.:

AF XY:

0.00488

AC XY:

663

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00282

AC:

3997

AN:

1417196

Hom.:

202

Cov.:

AF XY:

0.00235

AC XY:

1658

AN XY:

704582

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.00366

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000480

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.0284

AC:

4141

AN:

145804

Hom.:

194

Cov.:

AF XY:

0.0275

AC XY:

1939

AN XY:

70390

show subpopulations

Gnomad4 AFR

AF:

0.0996

Gnomad4 AMR

AF:

0.00793

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000150

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00202

Hom.:

Bravo

AF:

0.0319

ESP6500AA

AF:

0.101

AC:

444

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00867

AC:

1052

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.012

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.034

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.40

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.082

Sift

Benign

0.84

T;T

Sift4G

Benign

0.94

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.093

Gain of disorder (P = 0.0911);Gain of disorder (P = 0.0911);

MVP

0.29

MPC

0.11

ClinPred

0.031

GERP RS

4.1

Varity_R

0.044

gMVP

0.053

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