rs7220048

Positions:

• chr17-81144773-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080395.3(AATK):​c.56-10272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,144 control chromosomes in the GnomAD database, including 18,471 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18471 hom., cov: 34)
• Consequence: AATK NM_001080395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AATK	NM_001080395.3	c.56-10272A>G		intron_variant		ENST00000326724.9	NP_001073864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AATK	ENST00000326724.9	c.56-10272A>G		intron_variant		5	NM_001080395.3	ENSP00000324196	A2
AATK	ENST00000374792.6	c.56-10272A>G		intron_variant, NMD_transcript_variant		2		ENSP00000363924
AATK	ENST00000572798.1	n.274-10272A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74224 AN: 152026 Hom.: 18454 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74279 AN: 152144 Hom.: 18471 Cov.: 34 AF XY: 0.482 AC XY: 35836 AN XY: 74374

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.467

Alfa AF: 0.483 Hom.: 22675

Bravo AF: 0.495

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs7220048; hg19: chr17-79118573;