rs377052710

Variant names:

• chr9-108952478-A-C
• NM_003798.4:c.1646T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-108952478-A-C
• chr9-108952478-A-T

Variant summary

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

The NM_003798.4(CTNNAL1):​c.1646T>G​(p.Leu549Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L549Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CTNNAL1 NM_003798.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.66

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]

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=0.20725194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNAL1	NM_003798.4	c.1646T>G	p.Leu549Arg	missense_variant	Exon 13 of 19	ENST00000325551.9	NP_003789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNAL1	ENST00000325551.9	c.1646T>G	p.Leu549Arg	missense_variant	Exon 13 of 19	1	NM_003798.4	ENSP00000320434.4
CTNNAL1	ENST00000374595.8	c.1646T>G	p.Leu549Arg	missense_variant	Exon 13 of 19	1		ENSP00000363723.4
CTNNAL1	ENST00000374594.1	c.-152T>G		5_prime_UTR_variant	Exon 2 of 8	3		ENSP00000363722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.083
Sift	Benign	0.45	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.56	P;P
Vest4		0.38
MutPred		0.31		Gain of MoRF binding (P = 0.0103);Gain of MoRF binding (P = 0.0103);
MVP		0.55
MPC		0.65
ClinPred		0.90	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr9-111714758;