Variant 12-19439760-C-T 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.61C>T(p.Pro21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,517,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

AEBP2
NM_153207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.334

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=0.10171184).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP2	NM_153207.5 link	c.61C>T	p.Pro21Ser	missense_variant	1/8	ENST00000266508.14	NP_694939.2	Q6ZN18-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AEBP2	ENST00000266508.14 link	c.61C>T	p.Pro21Ser	missense_variant	1/8	1	NM_153207.5	ENSP00000266508.9	Q6ZN18-2
AEBP2	ENST00000398864.7 link	c.61C>T	p.Pro21Ser	missense_variant	1/9	1		ENSP00000381840.3	Q6ZN18-1
AEBP2	ENST00000541908.5 link	c.-16-22750C>T		intron_variant		3		ENSP00000437983.1	G5EA50
AEBP2	ENST00000538425.5 link	c.-16-22750C>T		intron_variant		4		ENSP00000444255.1	F5GZR7

Frequencies

GnomAD3 genomes

AF:

0.0000924

AC:

AN:

151592

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000457

AC:

AN:

109362

Hom.:

AF XY:

0.0000492

AC XY:

AN XY:

61002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000863

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:

0.0000767

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000208

AC:

284

AN:

1365324

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

151

AN XY:

673736

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000865

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000242

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.0000923

AC:

AN:

151706

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000102

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

May 24, 2023

The c.61C>T (p.P21S) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the proline (P) at amino acid position 21 to be replaced by a serine (S). 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

0.091

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.78

T;T

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.048

Sift

Benign

0.40

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;.

Vest4

0.065

MutPred

0.19

Gain of phosphorylation at P21 (P = 0.0035);Gain of phosphorylation at P21 (P = 0.0035);

MVP

0.093

MPC

1.1

ClinPred

0.13

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.25

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