Variant chr19-17281928-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152363.6(ANKLE1):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,382,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ANKLE1
NM_152363.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.445

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:

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

USHBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07183248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKLE1	NM_152363.6 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant	1/9	ENST00000404085.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKLE1	ENST00000404085.7 linkuse as main transcript	c.8C>T	p.Ser3Leu	missense_variant	1/9	2	NM_152363.6	P2	Q8NAG6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

131718

Hom.:

AF XY:

0.0000279

AC XY:

AN XY:

71768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000443

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1382318

Hom.:

Cov.:

AF XY:

0.0000147

AC XY:

AN XY:

681940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000240

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

Sep 25, 2023

The c.8C>T (p.S3L) alteration is located in exon 1 (coding exon 1) of the ANKLE1 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a leucine (L). 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

-0.33

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.63

T;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.76

REVEL

Benign

0.047

Sift4G

Uncertain

0.023

D;D

Vest4

0.10

MVP

0.27

MPC

0.41

ClinPred

0.60

GERP RS

1.2

gMVP

0.31

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