Variant 12-19440102-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153207.5(AEBP2):c.403G>T(p.Asp135Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,355,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000030 ( 0 hom. )

Consequence

AEBP2
NM_153207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

AEBP2 (HGNC:24051): (AE binding protein 2) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of transcription, DNA-templated. Located in nucleoplasm. Part of ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]

AEBP2 links:

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ACMG classification

Classification made for transcript

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=0.2330668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP2	NM_153207.5 linkuse as main transcript	c.403G>T	p.Asp135Tyr	missense_variant	1/8	ENST00000266508.14	NP_694939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AEBP2	ENST00000266508.14 linkuse as main transcript	c.403G>T	p.Asp135Tyr	missense_variant	1/8	1	NM_153207.5	ENSP00000266508		Q6ZN18-2
AEBP2	ENST00000398864.7 linkuse as main transcript	c.403G>T	p.Asp135Tyr	missense_variant	1/9	1		ENSP00000381840	P1	Q6ZN18-1
AEBP2	ENST00000538425.5 linkuse as main transcript	c.-16-22408G>T		intron_variant		4		ENSP00000444255
AEBP2	ENST00000541908.5 linkuse as main transcript	c.-16-22408G>T		intron_variant		3		ENSP00000437983

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1355688

Hom.:

Cov.:

AF XY:

0.00000449

AC XY:

AN XY:

668108

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000375

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 26, 2023

The c.403G>T (p.D135Y) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a G to T substitution at nucleotide position 403, causing the aspartic acid (D) at amino acid position 135 to be replaced by a tyrosine (Y). 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

0.18

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.081

T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.82

T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

1.0

D;.

Vest4

0.18

MutPred

0.25

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.18

MPC

1.3

ClinPred

0.62

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

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