2-219230375-C-CT

Variant names:

• chr2-219230375-C-CT
• rs776125621
• NM_018089.3:c.119dupT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018089.3(ANKZF1):​c.119dupT​(p.Ala41GlyfsTer38) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANKZF1 NM_018089.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.143
• Publications: 0 publications found

Genes affected

ANKZF1 (HGNC:25527): (ankyrin repeat and zinc finger peptidyl tRNA hydrolase 1) Predicted to enable metal ion binding activity. Involved in cellular response to hydrogen peroxide. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKZF1 Gene-Disease associations (from GenCC):

• inflammatory bowel disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018089.3. 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
	ANKZF1	NM_018089.3	MANE Select	c.119dupT	p.Ala41GlyfsTer38	frameshift	Exon 2 of 14	NP_060559.2	Q9H8Y5
	ANKZF1	NM_001042410.2		c.119dupT	p.Ala41GlyfsTer38	frameshift	Exon 2 of 14	NP_001035869.1	Q9H8Y5
	ANKZF1	NM_001282792.2		c.-267+476dupT		intron	N/A	NP_001269721.1	B8ZZS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKZF1	ENST00000323348.10	TSL:1 MANE Select	c.119dupT	p.Ala41GlyfsTer38	frameshift	Exon 2 of 14	ENSP00000321617.5	Q9H8Y5
	ANKZF1	ENST00000409849.5	TSL:1	c.-267+476dupT		intron	N/A	ENSP00000386815.1	B8ZZS4
	ANKZF1	ENST00000464763.5	TSL:1	n.267dupT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247342 AF XY: 0.00000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459640 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725790

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110474

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=48/152	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs776125621; hg19: chr2-220095097;