rs758109052

Positions:

• chr19-17286688-GTGTT-G
• chr19-17286688-GTGTT-GTGTTTGTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_152363.6(ANKLE1):​c.*140_*143del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 902,542 control chromosomes in the GnomAD database, including 3,277 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (1866 hom., cov: 0)
  • Exomes 𝑓: 0.17 (1411 hom.)
• Consequence: ANKLE1 NM_152363.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-17286688-GTGTT-G is Benign according to our data. Variant chr19-17286688-GTGTT-G is described in ClinVar as [Benign]. Clinvar id is 402369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKLE1	NM_152363.6	c.*140_*143del		3_prime_UTR_variant	9/9	ENST00000404085.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKLE1	ENST00000404085.7	c.*140_*143del		3_prime_UTR_variant	9/9	2	NM_152363.6	P2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 22635 AN: 100914 Hom.: 1860 Cov.: 0

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.134 AC: 8740 AN: 65312 Hom.: 160 AF XY: 0.132 AC XY: 4485 AN XY: 33936

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0246

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.167 AC: 133631 AN: 801554 Hom.: 1411 AF XY: 0.170 AC XY: 65720 AN XY: 386214

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.224 AC: 22650 AN: 100988 Hom.: 1866 Cov.: 0 AF XY: 0.219 AC XY: 10750 AN XY: 49104

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.253

Alfa AF: 0.151 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, Frequency -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs758109052; hg19: chr19-17397497;