Variant rs371454519 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278444.2(ANKLE1):c.1763G>T(p.Cys588Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,012,124 control chromosomes in the GnomAD database, including 1,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 565 hom., cov: 26)

Exomes 𝑓: 0.13 ( 893 hom. )

Consequence

ANKLE1
NM_001278444.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.223

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:

ANKLE1 (HGNC:):

ANKLE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-17286684-G-T is Benign according to our data. Variant chr19-17286684-G-T is described in ClinVar as [Benign]. Clinvar id is 402368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKLE1	NM_152363.6 linkuse as main transcript	c.*132G>T		3_prime_UTR_variant	9/9	ENST00000404085.7	NP_689576.6	Q8NAG6-2A0A499FJM0B4E124

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKLE1	ENST00000404085.7 linkuse as main transcript	c.*132G>T		3_prime_UTR_variant	9/9	2	NM_152363.6	ENSP00000384008.3		Q8NAG6-2

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

11660

AN:

114518

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0899

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.00206

Gnomad SAS

AF:

0.0393

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0805

AC:

5869

AN:

72870

Hom.:

119

AF XY:

0.0801

AC XY:

3057

AN XY:

38158

show subpopulations

Gnomad AFR exome

AF:

0.0519

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.0888

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.129

AC:

116096

AN:

897520

Hom.:

893

Cov.:

AF XY:

0.128

AC XY:

55880

AN XY:

438002

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.0640

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.00150

Gnomad4 SAS exome

AF:

0.0520

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.102

AC:

11667

AN:

114604

Hom.:

565

Cov.:

AF XY:

0.0987

AC XY:

5505

AN XY:

55762

show subpopulations

Gnomad4 AFR

AF:

0.0693

Gnomad4 AMR

AF:

0.0897

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.00206

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.0963

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0819

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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