dbSNP rs756766921: ANKLE1:p.Pro150Thr (chr19-17282990-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152363.6(ANKLE1):c.448C>A(p.Pro150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,410,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P150A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ANKLE1
NM_152363.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.499

Publications

0 publications found

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:

ENSG00000269307 (HGNC:):

ENSG00000269307 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05779323).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKLE1	NM_152363.6	MANE Select	c.448C>A	p.Pro150Thr	missense	Exon 4 of 9	NP_689576.6
ANKLE1	NM_001278444.2		c.448C>A	p.Pro150Thr	missense	Exon 4 of 8	NP_001265373.2
ANKLE1	NM_001278443.2		c.415C>A	p.Pro139Thr	missense	Exon 4 of 9	NP_001265372.2	A0A494C092

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKLE1	ENST00000404085.7	TSL:2 MANE Select	c.448C>A	p.Pro150Thr	missense	Exon 4 of 9	ENSP00000384008.3	Q8NAG6-2
ANKLE1	ENST00000394458.7	TSL:1	c.610C>A	p.Pro204Thr	missense	Exon 4 of 9	ENSP00000377971.4	A0A499FJM0
ANKLE1	ENST00000598347.2	TSL:2	c.448C>A	p.Pro150Thr	missense	Exon 4 of 8	ENSP00000470895.2	M0R002

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

172814

AF XY:

0.0000106

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000263

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000496

AC:

AN:

1410002

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32608

American (AMR)

AF:

0.00

AC:

AN:

38262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25394

East Asian (EAS)

AF:

0.00

AC:

AN:

37456

South Asian (SAS)

AF:

0.00

AC:

AN:

81040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000549

AC:

AN:

1092502

Other (OTH)

AF:

0.0000170

AC:

AN:

58824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000252

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.8

(source)

DANN

Benign

0.58

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.46

M_CAP

Benign

0.0018

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.97

PhyloP100

-0.50

PrimateAI

Benign

0.25

REVEL

Benign

0.21

Sift4G

Benign

0.11

Vest4

0.15

MVP

0.16

MPC

0.20

ClinPred

0.024

GERP RS

-0.84

PromoterAI

-0.0020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over