rs1002446579

Variant names:

• chr2-219230273-G-C
• rs1002446579
• NM_018089.3:c.16G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018089.3(ANKZF1):​c.16G>C​(p.Asp6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ANKZF1 NM_018089.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062380433).

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.16G>C	p.Asp6His	missense	Exon 2 of 14	NP_060559.2	Q9H8Y5
	ANKZF1	NM_001042410.2		c.16G>C	p.Asp6His	missense	Exon 2 of 14	NP_001035869.1	Q9H8Y5
	ANKZF1	NM_001282792.2		c.-267+373G>C		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.16G>C	p.Asp6His	missense	Exon 2 of 14	ENSP00000321617.5	Q9H8Y5
	ANKZF1	ENST00000409849.5	TSL:1	c.-267+373G>C		intron	N/A	ENSP00000386815.1	B8ZZS4
	ANKZF1	ENST00000464763.5	TSL:1	n.164G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.36
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.016
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.29	B
Vest4		0.22
MutPred		0.11		Loss of solvent accessibility (P = 0.0217)
MVP		0.44
MPC		0.14
ClinPred		0.10	T
GERP RS		3.5
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.35
Mutation Taster		=98/2	polymorphism

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: rs1002446579; hg19: chr2-220094995;