chr1-25835029-G-C

Position:

• chr1-25835029-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000374298.4(AUNIP):​c.1038C>G​(p.Asp346Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AUNIP ENST00000374298.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.274

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUNIP	NM_024037.3	c.1038C>G	p.Asp346Glu	missense_variant	3/3	ENST00000374298.4	NP_076942.1
AUNIP	NM_001287490.2	c.1038C>G	p.Asp346Glu	missense_variant	3/4		NP_001274419.1
AUNIP	XM_047430116.1	c.933C>G	p.Asp311Glu	missense_variant	3/3		XP_047286072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUNIP	ENST00000374298.4	c.1038C>G	p.Asp346Glu	missense_variant	3/3	1	NM_024037.3	ENSP00000363416	P1
AUNIP	ENST00000538789.5	c.1038C>G	p.Asp346Glu	missense_variant	3/4	1		ENSP00000443647
AUNIP	ENST00000481602.1	n.136-698C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.1038C>G (p.D346E) alteration is located in exon 3 (coding exon 3) of the AUNIP gene. This alteration results from a C to G substitution at nucleotide position 1038, causing the aspartic acid (D) at amino acid position 346 to be replaced by a glutamic acid (E). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.75	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.84
MutPred		0.39		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.60
MPC		0.48
ClinPred		1.0	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.11

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.

Other links and lift over

hg19: chr1-26161520;