19-17286688-GTGTT-GTGTTTGTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278444.2(ANKLE1):​c.1771_1774dupTTGT​(p.Cys592PhefsTer34) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: ANKLE1 NM_001278444.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• 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: Uncertain_significance. The variant received 0 ACMG points.

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_*143dupTTGT		3_prime_UTR	Exon 9 of 9	NP_689576.6
	ANKLE1	NM_001278444.2		c.1771_1774dupTTGT	p.Cys592PhefsTer34	frameshift	Exon 8 of 8	NP_001265373.2
	ANKLE1	NM_001278443.2		c.*140_*143dupTTGT		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_*143dupTTGT		3_prime_UTR	Exon 9 of 9	ENSP00000384008.3	Q8NAG6-2
	ANKLE1	ENST00000394458.7	TSL:1	c.*140_*143dupTTGT		3_prime_UTR	Exon 9 of 9	ENSP00000377971.4	A0A499FJM0
	ANKLE1	ENST00000598347.2	TSL:2	c.1771_1774dupTTGT	p.Cys592fs	frameshift	Exon 8 of 8	ENSP00000470895.2	M0R002

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs758109052; hg19: chr19-17397497;