5-138932622-A-T

Position:

• chr5-138932622-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001903.5(CTNNA1):​c.2343A>T​(p.Gln781His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q781Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTNNA1 NM_001903.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

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
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNA1	NM_001903.5	c.2343A>T	p.Gln781His	missense_variant	17/18	ENST00000302763.12	NP_001894.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNA1	ENST00000302763.12	c.2343A>T	p.Gln781His	missense_variant	17/18	1	NM_001903.5	ENSP00000304669.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;D;T;.
Eigen	Benign	0.090
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T;T;.;T
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	.;M;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	.;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	.;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.97	D;P;D;.
Vest4		0.83
MutPred		0.59		Loss of catalytic residue at Q781 (P = 0.0022);Loss of catalytic residue at Q781 (P = 0.0022);Loss of catalytic residue at Q781 (P = 0.0022);.;
MVP		0.83
MPC		2.0
ClinPred		0.97	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.81
gMVP		0.80

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: chr5-138268311;