14-22981970-C-G

Position:

• chr14-22981970-C-G

Variant summary

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

The NM_032876.6(AJUBA):​c.297G>C​(p.Leu99Phe) 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. 13/20 in silico tools predict 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: 1.30

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]

ENSG00000259132 (HGNC:):

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=0.21920717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJUBA	NM_032876.6	c.297G>C	p.Leu99Phe	missense_variant	1/8	ENST00000262713.7	NP_116265.1
AJUBA	NM_001289097.2	c.297G>C	p.Leu99Phe	missense_variant	1/2		NP_001276026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJUBA	ENST00000262713.7	c.297G>C	p.Leu99Phe	missense_variant	1/8	1	NM_032876.6	ENSP00000262713.2
ENSG00000259132	ENST00000555074.1	c.49+239G>C		intron_variant		2		ENSP00000450856.2

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

Oct 13, 2023

The c.297G>C (p.L99F) alteration is located in exon 1 (coding exon 1) of the AJUBA gene. This alteration results from a G to C substitution at nucleotide position 297, causing the leucine (L) at amino acid position 99 to be replaced by a phenylalanine (F). 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	0.075
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.0091
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.70	.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.090
Sift	Benign	0.051	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.94	P;P
Vest4		0.18
MutPred		0.26		Gain of catalytic residue at P94 (P = 0.0099);Gain of catalytic residue at P94 (P = 0.0099);
MVP		0.45
ClinPred		0.79	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.090
gMVP		0.13

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: chr14-23451179;