Variant 17-81119451-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080395.3(AATK):c.4013C>T(p.Thr1338Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 1,364,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

AATK
NM_001080395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

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:

AATK (HGNC:):

AATK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AATK	NM_001080395.3 linkuse as main transcript	c.4013C>T	p.Thr1338Met	missense_variant	13/14	ENST00000326724.9	NP_001073864.2	Q6ZMQ8-1
AATK	NM_004920.3 linkuse as main transcript	c.3704C>T	p.Thr1235Met	missense_variant	12/13		NP_004911.2	Q6ZMQ8H7C175

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATK	ENST00000326724.9 linkuse as main transcript	c.4013C>T	p.Thr1338Met	missense_variant	13/14	5	NM_001080395.3	ENSP00000324196.4		Q6ZMQ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000660

AC:

AN:

1364654

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

674160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000297

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.00000374

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000168

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

Oct 30, 2023

The c.4013C>T (p.T1338M) alteration is located in exon 13 (coding exon 13) of the AATK gene. This alteration results from a C to T substitution at nucleotide position 4013, causing the threonine (T) at amino acid position 1338 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.7

D;.

REVEL

Benign

0.16

Sift

Benign

0.040

D;.

Sift4G

Benign

0.064

T;T

Polyphen

1.0

D;.

Vest4

0.56

MutPred

0.28

Loss of glycosylation at T1338 (P = 0.0043);.;

MVP

0.47

MPC

0.74

ClinPred

0.88

GERP RS

3.5

Varity_R

0.19

gMVP

0.29

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