Variant 1-25835414-G-A 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_024037.3(AUNIP):c.653C>T(p.Pro218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AUNIP
NM_024037.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

Variant links:

Genes affected

AUNIP (HGNC:28363): (aurora kinase A and ninein interacting protein) Enables damaged DNA binding activity. Involved in double-strand break repair via homologous recombination; negative regulation of double-strand break repair via nonhomologous end joining; and spindle organization. Located in centrosome; site of DNA damage; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

AUNIP links:

AUNIP (HGNC:):

AUNIP 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=0.10222891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUNIP	NM_024037.3 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	3/3	ENST00000374298.4	NP_076942.1	Q9H7T9-1
AUNIP	NM_001287490.2 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	3/4		NP_001274419.1	Q9H7T9-2
AUNIP	XM_047430116.1 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	3/3		XP_047286072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AUNIP	ENST00000374298.4 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	3/3	1	NM_024037.3	ENSP00000363416.4	Q9H7T9-1
AUNIP	ENST00000538789.5 linkuse as main transcript	c.653C>T	p.Pro218Leu	missense_variant	3/4	1		ENSP00000443647.1	Q9H7T9-2
AUNIP	ENST00000481602.1 linkuse as main transcript	n.136-1083C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 20, 2024

The c.653C>T (p.P218L) alteration is located in exon 3 (coding exon 3) of the AUNIP gene. This alteration results from a C to T substitution at nucleotide position 653, causing the proline (P) at amino acid position 218 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

0.079

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

DANN

Benign

0.72

DEOGEN2

Benign

0.055

.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.041

Sift

Uncertain

0.027

D;D

Sift4G

Benign

0.085

T;T

Polyphen

0.0010

.;B

Vest4

0.12

MutPred

0.19

Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);

MVP

0.21

MPC

0.13

ClinPred

0.097

GERP RS

0.044

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.029

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over