Variant 4-128861842-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_199320.4(JADE1):c.1120C>A(p.Pro374Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

JADE1
NM_199320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430

Variant links:

Genes affected

JADE1 (HGNC:30027): (jade family PHD finger 1) Enables transcription coactivator activity. Involved in histone acetylation and negative regulation of canonical Wnt signaling pathway. Acts upstream of or within negative regulation of G1/S transition of mitotic cell cycle. Located in several cellular components, including ciliary basal body; cytosol; and nuclear speck. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

JADE1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04718113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE1	NM_199320.4 linkuse as main transcript	c.1120C>A	p.Pro374Thr	missense_variant	9/11	ENST00000226319.11	NP_955352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE1	ENST00000226319.11 linkuse as main transcript	c.1120C>A	p.Pro374Thr	missense_variant	9/11	5	NM_199320.4	ENSP00000226319	P1	Q6IE81-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.1120C>A (p.P374T) alteration is located in exon 9 (coding exon 8) of the JADE1 gene. This alteration results from a C to A substitution at nucleotide position 1120, causing the proline (P) at amino acid position 374 to be replaced by a threonine (T). 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

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.1

DANN

Benign

0.64

DEOGEN2

Benign

0.036

T;.;.;T;T;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.72

T;.;T;.;.;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.047

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.55

N;N;N;N;.;N;.

REVEL

Benign

0.041

Sift

Benign

0.15

T;T;T;T;.;T;.

Sift4G

Benign

0.32

T;T;T;T;T;T;T

Polyphen

0.0030

B;B;B;B;B;B;B

Vest4

0.058

MutPred

0.15

Gain of glycosylation at S370 (P = 0.0043);Gain of glycosylation at S370 (P = 0.0043);.;Gain of glycosylation at S370 (P = 0.0043);Gain of glycosylation at S370 (P = 0.0043);Gain of glycosylation at S370 (P = 0.0043);Gain of glycosylation at S370 (P = 0.0043);

MVP

0.19

MPC

0.78

ClinPred

0.032

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.40

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over