dbSNP rs765068179: ANKLE1:p.Arg126Gln (chr19-17282919-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152363.6(ANKLE1):c.377G>A(p.Arg126Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKLE1
NM_152363.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.231

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11393285).

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.377G>A	p.Arg126Gln	missense	Exon 4 of 9	NP_689576.6
ANKLE1	NM_001278444.2		c.377G>A	p.Arg126Gln	missense	Exon 4 of 8	NP_001265373.2
ANKLE1	NM_001278443.2		c.344G>A	p.Arg115Gln	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.377G>A	p.Arg126Gln	missense	Exon 4 of 9	ENSP00000384008.3	Q8NAG6-2
ANKLE1	ENST00000394458.7	TSL:1	c.539G>A	p.Arg180Gln	missense	Exon 4 of 9	ENSP00000377971.4	A0A499FJM0
ENSG00000269307	ENST00000596542.1	TSL:2	n.*710G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1420442

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32912

American (AMR)

AF:

0.00

AC:

AN:

39244

Ashkenazi Jewish (ASJ)

AF:

0.0000392

AC:

AN:

25508

East Asian (EAS)

AF:

0.00

AC:

AN:

38012

South Asian (SAS)

AF:

0.00

AC:

AN:

81982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097254

Other (OTH)

AF:

0.00

AC:

AN:

59188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.48

M_CAP

Benign

0.066

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

0.23

PrimateAI

Benign

0.25

REVEL

Benign

0.031

Sift4G

Benign

0.62

Vest4

0.21

MVP

0.33

MPC

0.65

ClinPred

0.36

GERP RS

-0.69

PromoterAI

0.022

Neutral

(source)

gMVP

0.10

Mutation Taster

=95/5

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

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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