9-108943981-A-C

Position:

• chr9-108943981-A-C

Variant summary

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

The NM_003798.4(CTNNAL1):​c.1922T>G​(p.Val641Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNAL1 NM_003798.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18

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]

ABITRAM (HGNC:1364): (actin binding transcription modulator) Predicted to enable actin filament binding activity and actin monomer binding activity. Predicted to be involved in dendrite morphogenesis; regulation of actin filament polymerization; and regulation of filopodium assembly. Predicted to be located in growth cone. Predicted to be active in several cellular components, including dendrite; filopodium tip; and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

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	Protein	UniProt
CTNNAL1	NM_003798.4	c.1922T>G	p.Val641Gly	missense_variant	16/19	ENST00000325551.9	NP_003789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNAL1	ENST00000325551.9	c.1922T>G	p.Val641Gly	missense_variant	16/19	1	NM_003798.4	ENSP00000320434.4
CTNNAL1	ENST00000374595.8	c.1922T>G	p.Val641Gly	missense_variant	16/19	1		ENSP00000363723.4
CTNNAL1	ENST00000374594.1	c.125T>G	p.Val42Gly	missense_variant	5/8	3		ENSP00000363722.1
ABITRAM	ENST00000374624.7	c.262-6526A>C		intron_variant		3		ENSP00000363754.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.1922T>G (p.V641G) alteration is located in exon 16 (coding exon 16) of the CTNNAL1 gene. This alteration results from a T to G substitution at nucleotide position 1922, causing the valine (V) at amino acid position 641 to be replaced by a glycine (G). 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	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.76	P;B;.
Vest4		0.55
MutPred		0.63		Gain of disorder (P = 0.0119);Gain of disorder (P = 0.0119);.;
MVP		0.51
MPC		0.28
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.53
gMVP		0.40

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: chr9-111706261;