Variant 17-36949186-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000619387.5(AATF):c.61G>C(p.Glu21Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,593,784 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

AATF
ENST00000619387.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Variant links:

Genes affected

AATF (HGNC:19235): (apoptosis antagonizing transcription factor) The protein encoded by this gene was identified on the basis of its interaction with MAP3K12/DLK, a protein kinase known to be involved in the induction of cell apoptosis. This gene product contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis. [provided by RefSeq, Jul 2008]

AATF 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=0.22235474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AATF	NM_012138.4 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	1/12	ENST00000619387.5	NP_036270.1
AATF	NM_001411094.1 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	1/11		NP_001398023.1
AATF	XM_047435748.1 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	1/5		XP_047291704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATF	ENST00000619387.5 linkuse as main transcript	c.61G>C	p.Glu21Gln	missense_variant	1/12	1	NM_012138.4	ENSP00000477848	P2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1441504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715020

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:

0.00000453

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000835

AC:

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

Dec 14, 2022

The c.61G>C (p.E21Q) alteration is located in exon 1 (coding exon 1) of the AATF gene. This alteration results from a G to C substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Benign

0.72

M_CAP

Benign

0.0069

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.77

Sift4G

Benign

0.57

Polyphen

0.99

Vest4

0.18

MutPred

0.11

Gain of glycosylation at P19 (P = 0.2599);

MVP

0.51

ClinPred

0.93

GERP RS

5.8

Varity_R

0.17

gMVP

0.099

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