Variant 12-19439947-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153207.5(AEBP2):c.248C>G(p.Ser83Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,513,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

AEBP2
NM_153207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24576944).

BS2

High AC in GnomAd at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AEBP2	NM_153207.5 linkuse as main transcript	c.248C>G	p.Ser83Trp	missense_variant	1/8	ENST00000266508.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AEBP2	ENST00000266508.14 linkuse as main transcript	c.248C>G	p.Ser83Trp	missense_variant	1/8	1	NM_153207.5		Q6ZN18-2
AEBP2	ENST00000398864.7 linkuse as main transcript	c.248C>G	p.Ser83Trp	missense_variant	1/9	1		P1	Q6ZN18-1
AEBP2	ENST00000538425.5 linkuse as main transcript	c.-16-22563C>G		intron_variant		4
AEBP2	ENST00000541908.5 linkuse as main transcript	c.-16-22563C>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000804

AC:

AN:

149258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000496

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:

0.000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000532

AC:

AN:

112710

Hom.:

AF XY:

0.0000807

AC XY:

AN XY:

61966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

138

AN:

1364254

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

673154

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:

0.0000293

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000351

GnomAD4 genome

AF:

0.0000804

AC:

AN:

149258

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72780

show subpopulations

Gnomad4 AFR

AF:

0.0000496

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000793

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.248C>G (p.S83W) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a C to G substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by a tryptophan (W). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.87

D;D

M_CAP

Pathogenic

1.0

MetaRNN

Benign

0.25

T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;.

Vest4

0.35

MutPred

0.16

Loss of phosphorylation at S83 (P = 0.0031);Loss of phosphorylation at S83 (P = 0.0031);

MVP

0.22

MPC

1.5

ClinPred

0.31

GERP RS

4.0

Varity_R

0.20

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over