Variant 17-81119512-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080395.3(AATK):c.3952G>A(p.Asp1318Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,564,296 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 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

AATK
NM_001080395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

AATK (HGNC:21): (apoptosis associated tyrosine kinase) The protein encoded by this gene contains a tyrosine kinase domain at the N-terminus and a proline-rich domain at the C-terminus. This gene is induced during apoptosis, and expression of this gene may be a necessary pre-requisite for the induction of growth arrest and/or apoptosis of myeloid precursor cells. This gene has been shown to produce neuronal differentiation in a neuroblastoma cell line. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

AATK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034148633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AATK	NM_001080395.3 linkuse as main transcript	c.3952G>A	p.Asp1318Asn	missense_variant	13/14	ENST00000326724.9	NP_001073864.2
AATK	NM_004920.3 linkuse as main transcript	c.3643G>A	p.Asp1215Asn	missense_variant	12/13		NP_004911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATK	ENST00000326724.9 linkuse as main transcript	c.3952G>A	p.Asp1318Asn	missense_variant	13/14	5	NM_001080395.3	ENSP00000324196	A2	Q6ZMQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000262

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000170

AC:

AN:

182814

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

100858

show subpopulations

Gnomad AFR exome

AF:

0.000227

Gnomad AMR exome

AF:

0.000407

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:

0.000188

Gnomad OTH exome

AF:

0.000450

GnomAD4 exome

AF:

0.000237

AC:

335

AN:

1412396

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

175

AN XY:

699766

show subpopulations

Gnomad4 AFR exome

AF:

0.0000338

Gnomad4 AMR exome

AF:

0.000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000279

Gnomad4 OTH exome

AF:

0.000188

GnomAD4 genome

AF:

0.0000987

AC:

AN:

151900

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.000152

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

Jul 25, 2023

The c.3952G>A (p.D1318N) alteration is located in exon 13 (coding exon 13) of the AATK gene. This alteration results from a G to A substitution at nucleotide position 3952, causing the aspartic acid (D) at amino acid position 1318 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0043

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.81

N;.

REVEL

Benign

0.035

Sift

Benign

0.086

T;.

Sift4G

Benign

0.40

T;T

Polyphen

0.12

B;.

Vest4

0.14

MVP

0.20

MPC

0.23

ClinPred

0.027

GERP RS

2.5

Varity_R

0.034

gMVP

0.087

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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