rs1060502219

Positions:

• chr5-138917856-G-A
• chr5-138917856-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001903.5(CTNNA1):​c.1504G>A​(p.Val502Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V502L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTNNA1 NM_001903.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

Genes affected

CTNNA1 (HGNC:2509): (catenin alpha 1) This gene encodes a member of the catenin family of proteins that play an important role in cell adhesion process by connecting cadherins located on the plasma membrane to the actin filaments inside the cell. The encoded mechanosensing protein contains three vinculin homology domains and undergoes conformational changes in response to cytoskeletal tension, resulting in the reconfiguration of cadherin-actin filament connections. Certain mutations in this gene cause butterfly-shaped pigment dystrophy. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CTNNA1. . Gene score misZ 3.6624 (greater than the threshold 3.09). Trascript score misZ 4.1669 (greater than threshold 3.09). GenCC has associacion of gene with patterned macular dystrophy 2, CTNNA1-related diffuse gastric and lobular breast cancer syndrome, patterned macular dystrophy, hereditary nonpolyposis colon cancer.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNNA1	NM_001903.5	c.1504G>A	p.Val502Ile	missense_variant	11/18	ENST00000302763.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNNA1	ENST00000302763.12	c.1504G>A	p.Val502Ile	missense_variant	11/18	1	NM_001903.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	0.0022	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;.;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.8	.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.83	.;N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	.;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.39	B;B;B;.
Vest4		0.50
MutPred		0.69		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;
MVP		0.62
MPC		1.2
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.47

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: chr5-138253545;