12-19440102-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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]

ACMG classification

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	UniProt
AEBP2	NM_153207.5	c.403G>T	p.Asp135Tyr	missense_variant	1/8	ENST00000266508.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AEBP2	ENST00000266508.14	c.403G>T	p.Asp135Tyr	missense_variant	1/8	1	NM_153207.5
AEBP2	ENST00000398864.7	c.403G>T	p.Asp135Tyr	missense_variant	1/9	1		P1
AEBP2	ENST00000538425.5	c.-16-22408G>T		intron_variant		4
AEBP2	ENST00000541908.5	c.-16-22408G>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000295 AC: 4 AN: 1355688 Hom.: 0 Cov.: 35 AF XY: 0.00000449 AC XY: 3 AN XY: 668108

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.19
Cadd	Uncertain	24
Dann	Benign	0.91
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Pathogenic	0.96	D
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	D
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.

Other links and lift over

hg19: chr12-19593036;