Variant chr1-25835525-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024037.3(AUNIP):c.542G>A(p.Ser181Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,614,136 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

AUNIP
NM_024037.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.118

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070996583).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUNIP	NM_024037.3 linkuse as main transcript	c.542G>A	p.Ser181Asn	missense_variant	3/3	ENST00000374298.4	NP_076942.1	Q9H7T9-1
AUNIP	NM_001287490.2 linkuse as main transcript	c.542G>A	p.Ser181Asn	missense_variant	3/4		NP_001274419.1	Q9H7T9-2
AUNIP	XM_047430116.1 linkuse as main transcript	c.437G>A	p.Ser146Asn	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.542G>A	p.Ser181Asn	missense_variant	3/3	1	NM_024037.3	ENSP00000363416.4	Q9H7T9-1
AUNIP	ENST00000538789.5 linkuse as main transcript	c.542G>A	p.Ser181Asn	missense_variant	3/4	1		ENSP00000443647.1	Q9H7T9-2
AUNIP	ENST00000481602.1 linkuse as main transcript	n.136-1194G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000613

AC:

154

AN:

251378

Hom.:

AF XY:

0.000648

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000950

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000586

AC:

856

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

452

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000654

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000703

AC:

107

AN:

152244

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000555

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000634

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000474

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

Dec 20, 2021

The c.542G>A (p.S181N) alteration is located in exon 3 (coding exon 3) of the AUNIP gene. This alteration results from a G to A substitution at nucleotide position 542, causing the serine (S) at amino acid position 181 to be replaced by an asparagine (N). 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

0.086

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.0

DANN

Benign

0.76

DEOGEN2

Benign

0.0058

.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.087

Sift

Benign

0.76

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.20

.;B

Vest4

0.19

MVP

0.33

MPC

0.38

ClinPred

0.011

GERP RS

0.29

Varity_R

0.029

gMVP

0.051

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