rs758109052

Variant names:

• chr19-17286688-GTGTT-G
• rs758109052
• NM_152363.6:c.*140_*143delTTGT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001278444.2(ANKLE1):​c.1771_1774delTTGT​(p.Leu591ValfsTer17) variant causes a frameshift 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_001278444.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278444.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKLE1	NM_152363.6	MANE Select	c.*140_*143delTTGT		3_prime_UTR	Exon 9 of 9	NP_689576.6
	ANKLE1	NM_001278444.2		c.1771_1774delTTGT	p.Leu591ValfsTer17	frameshift	Exon 8 of 8	NP_001265373.2
	ANKLE1	NM_001278443.2		c.*140_*143delTTGT		3_prime_UTR	Exon 9 of 9	NP_001265372.2	A0A494C092

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKLE1	ENST00000404085.7	TSL:2 MANE Select	c.*140_*143delTTGT		3_prime_UTR	Exon 9 of 9	ENSP00000384008.3	Q8NAG6-2
	ANKLE1	ENST00000394458.7	TSL:1	c.*140_*143delTTGT		3_prime_UTR	Exon 9 of 9	ENSP00000377971.4	A0A499FJM0
	ANKLE1	ENST00000598347.2	TSL:2	c.1771_1774delTTGT	p.Leu591fs	frameshift	Exon 8 of 8	ENSP00000470895.2	M0R002

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

GnomAD2 exomes AF: 0.134 AC: 8740 AN: 65312 AF XY: 0.132

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.173 AC: 2558 AN: 14752

American (AMR) AF: 0.164 AC: 2857 AN: 17464

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 3029 AN: 11548

East Asian (EAS) AF: 0.0307 AC: 587 AN: 19120

South Asian (SAS) AF: 0.175 AC: 6111 AN: 34870

European-Finnish (FIN) AF: 0.273 AC: 3093 AN: 11310

Middle Eastern (MID) AF: 0.218 AC: 648 AN: 2978

European-Non Finnish (NFE) AF: 0.166 AC: 109015 AN: 658340

Other (OTH) AF: 0.184 AC: 5733 AN: 31172

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.263 AC: 5375 AN: 20434

American (AMR) AF: 0.194 AC: 2218 AN: 11406

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 772 AN: 2630

East Asian (EAS) AF: 0.0247 AC: 83 AN: 3366

South Asian (SAS) AF: 0.145 AC: 519 AN: 3570

European-Finnish (FIN) AF: 0.146 AC: 951 AN: 6496

Middle Eastern (MID) AF: 0.282 AC: 66 AN: 234

European-Non Finnish (NFE) AF: 0.239 AC: 12114 AN: 50594

Other (OTH) AF: 0.253 AC: 365 AN: 1442

Alfa AF: 0.151 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
Mutation Taster		=191/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs758109052; hg19: chr19-17397497; COSMIC: COSV66729795; COSMIC: COSV66729795;