17-81119442-G-C

Position:

• chr17-81119442-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080395.3(AATK):​c.4022C>G​(p.Pro1341Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AATK NM_001080395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AATK	NM_001080395.3	c.4022C>G	p.Pro1341Arg	missense_variant	13/14	ENST00000326724.9	NP_001073864.2
AATK	NM_004920.3	c.3713C>G	p.Pro1238Arg	missense_variant	12/13		NP_004911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATK	ENST00000326724.9	c.4022C>G	p.Pro1341Arg	missense_variant	13/14	5	NM_001080395.3	ENSP00000324196.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 46

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

Sep 06, 2022

The c.4022C>G (p.P1341R) alteration is located in exon 13 (coding exon 13) of the AATK gene. This alteration results from a C to G substitution at nucleotide position 4022, causing the proline (P) at amino acid position 1341 to be replaced by an arginine (R). 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	0.28
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-7.3	D;.
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.45		Gain of MoRF binding (P = 0.0068);.;
MVP		0.28
MPC		0.75
ClinPred		1.0	D
GERP RS		3.5
Varity_R		0.66
gMVP		0.48

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: chr17-79093242;