9-108943808-G-C

Position:

• chr9-108943808-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000325551.9(CTNNAL1):​c.1950C>G​(p.Asp650Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNAL1 ENST00000325551.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15797925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNAL1	NM_003798.4	c.1950C>G	p.Asp650Glu	missense_variant	17/19	ENST00000325551.9	NP_003789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNAL1	ENST00000325551.9	c.1950C>G	p.Asp650Glu	missense_variant	17/19	1	NM_003798.4	ENSP00000320434	P1
CTNNAL1	ENST00000374595.8	c.1950C>G	p.Asp650Glu	missense_variant	17/19	1		ENSP00000363723
CTNNAL1	ENST00000374594.1	c.153C>G	p.Asp51Glu	missense_variant	6/8	3		ENSP00000363722
ABITRAM	ENST00000374624.7	c.262-6699G>C		intron_variant		3		ENSP00000363754

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

Jan 23, 2024

The c.1950C>G (p.D650E) alteration is located in exon 17 (coding exon 17) of the CTNNAL1 gene. This alteration results from a C to G substitution at nucleotide position 1950, causing the aspartic acid (D) at amino acid position 650 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Benign	0.0041	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;T;.
Eigen	Benign	-0.033
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	1.0	D;D;D;N;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.78	T;T;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.11	B;P;.
Vest4		0.21
MutPred		0.40		Gain of ubiquitination at K646 (P = 0.1067);Gain of ubiquitination at K646 (P = 0.1067);.;
MVP		0.51
MPC		0.17
ClinPred		0.82	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.080
gMVP		0.21

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: chr9-111706088;