rs528375709

Variant names:

• chr14-22981639-C-A
• rs528375709
• NM_032876.6:c.628G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22981639-C-A
• chr14-22981639-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032876.6(AJUBA):​c.628G>T​(p.Ala210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A210T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AJUBA NM_032876.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63
• Publications: 0 publications found

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:):

AJUBA-DT (HGNC:55449): (AJUBA divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20534497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032876.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJUBA	NM_032876.6	MANE Select	c.628G>T	p.Ala210Ser	missense	Exon 1 of 8	NP_116265.1	Q96IF1-1
	AJUBA	NM_001289097.2		c.628G>T	p.Ala210Ser	missense	Exon 1 of 2	NP_001276026.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJUBA	ENST00000262713.7	TSL:1 MANE Select	c.628G>T	p.Ala210Ser	missense	Exon 1 of 8	ENSP00000262713.2	Q96IF1-1
	ENSG00000259132	ENST00000555074.1	TSL:2	c.49+570G>T		intron	N/A	ENSP00000450856.2	G3V2T6
	AJUBA	ENST00000921862.1		c.628G>T	p.Ala210Ser	missense	Exon 1 of 7	ENSP00000591921.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1365978 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 671256

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 33260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23242

East Asian (EAS) AF: 0.00 AC: 0 AN: 36114

South Asian (SAS) AF: 0.00 AC: 0 AN: 75658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067378

Other (OTH) AF: 0.00 AC: 0 AN: 56832

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.019
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.051
Sift	Benign	0.085	T
Sift4G	Benign	0.39	T
Polyphen		0.61	P
Vest4		0.26
MutPred		0.32		Gain of catalytic residue at E206 (P = 0.0103)
MVP		0.49
ClinPred		0.57	D
GERP RS		4.6
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.29
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs528375709; hg19: chr14-23450848;