1-25835277-GTTTCACTGAT-G

Position:

• chr1-25835277-GTTTCACTGAT-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000374298.4(AUNIP):​c.780_789del​(p.Glu260AspfsTer47) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,614,114 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (31 hom.)
• Consequence: AUNIP ENST00000374298.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-25835277-GTTTCACTGAT-G is Benign according to our data. Variant chr1-25835277-GTTTCACTGAT-G is described in ClinVar as [Likely_benign]. Clinvar id is 782229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AUNIP	NM_024037.3	c.780_789del	p.Glu260AspfsTer47	frameshift_variant	3/3	ENST00000374298.4	NP_076942.1
AUNIP	NM_001287490.2	c.780_789del	p.Glu260AspfsTer47	frameshift_variant	3/4		NP_001274419.1
AUNIP	XM_047430116.1	c.675_684del	p.Glu225AspfsTer47	frameshift_variant	3/3		XP_047286072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUNIP	ENST00000374298.4	c.780_789del	p.Glu260AspfsTer47	frameshift_variant	3/3	1	NM_024037.3	ENSP00000363416	P1
AUNIP	ENST00000538789.5	c.780_789del	p.Glu260AspfsTer47	frameshift_variant	3/4	1		ENSP00000443647
AUNIP	ENST00000481602.1	n.136-956_136-947del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 646 AN: 152210 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00414 AC: 1041 AN: 251156 Hom.: 3 AF XY: 0.00410 AC XY: 557 AN XY: 135744

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00721

Gnomad NFE exome AF: 0.00621

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00529 AC: 7730 AN: 1461786 Hom.: 31 AF XY: 0.00518 AC XY: 3770 AN XY: 727198

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00225

Gnomad4 FIN exome AF: 0.00828

Gnomad4 NFE exome AF: 0.00603

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.00425 AC: 647 AN: 152328 Hom.: 3 Cov.: 32 AF XY: 0.00435 AC XY: 324 AN XY: 74484

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.00398

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00404 Hom.: 2

Bravo AF: 0.00342

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00567

EpiControl AF: 0.00575

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs564635111; hg19: chr1-26161768;