14-22981854-G-C

Position:

• chr14-22981854-G-C

Variant summary

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

The NM_032876.6(AJUBA):​c.413C>G​(p.Pro138Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AJUBA NM_032876.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

Genes affected

AJUBA (HGNC:20250): (ajuba LIM protein) Enables alpha-catenin binding activity and transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; positive regulation of gene silencing by miRNA; and regulation of cellular response to hypoxia. Acts upstream of or within gene silencing by miRNA and positive regulation of protein-containing complex assembly. Located in several cellular components, including Golgi apparatus; P-body; and nucleoplasm. [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=0.2202526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJUBA	NM_032876.6	c.413C>G	p.Pro138Arg	missense_variant	1/8	ENST00000262713.7	NP_116265.1
AJUBA	NM_001289097.2	c.413C>G	p.Pro138Arg	missense_variant	1/2		NP_001276026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJUBA	ENST00000262713.7	c.413C>G	p.Pro138Arg	missense_variant	1/8	1	NM_032876.6	ENSP00000262713	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 22, 2024

The c.413C>G (p.P138R) alteration is located in exon 1 (coding exon 1) of the AJUBA gene. This alteration results from a C to G substitution at nucleotide position 413, causing the proline (P) at amino acid position 138 to be replaced by an arginine (R). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	0.045
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	0.91	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.36	B;B
Vest4		0.33
MutPred		0.35		Gain of MoRF binding (P = 0.0086);Gain of MoRF binding (P = 0.0086);
MVP		0.44
ClinPred		0.82	D
GERP RS		4.6
Varity_R		0.14
gMVP		0.70

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: chr14-23451063;