Variant chr19-17282969-G-A 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_152363.6(ANKLE1):c.427G>A(p.Ala143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,566,486 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

ANKLE1
NM_152363.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.139

Variant links:

Genes affected

ANKLE1 (HGNC:26812): (ankyrin repeat and LEM domain containing 1) Enables endonuclease activity. Involved in positive regulation of response to DNA damage stimulus and protein export from nucleus. Located in cytosol and nucleoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKLE1 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=0.020049483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKLE1	NM_152363.6 linkuse as main transcript	c.427G>A	p.Ala143Thr	missense_variant	4/9	ENST00000404085.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKLE1	ENST00000404085.7 linkuse as main transcript	c.427G>A	p.Ala143Thr	missense_variant	4/9	2	NM_152363.6	P2	Q8NAG6-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000562

AC:

AN:

177792

Hom.:

AF XY:

0.0000824

AC XY:

AN XY:

97090

show subpopulations

Gnomad AFR exome

AF:

0.000780

Gnomad AMR exome

AF:

0.0000364

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:

0.0000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1414296

Hom.:

Cov.:

AF XY:

0.0000314

AC XY:

AN XY:

700698

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.0000775

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:

0.00

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.000158

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000555

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:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.0000503

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 08, 2021

The c.427G>A (p.A143T) alteration is located in exon 4 (coding exon 4) of the ANKLE1 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the alanine (A) at amino acid position 143 to be replaced by a threonine (T). 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

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.7

DANN

Uncertain

0.98

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.50

T;.

M_CAP

Benign

0.0090

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

REVEL

Benign

0.089

Sift4G

Benign

0.51

T;T

Vest4

0.042

MVP

0.18

MPC

0.17

ClinPred

0.075

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.15

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