Genetic Variant NM_018089.3:c.16G>C (chr2-219230273-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

Publications

0 publications found

Variant links:

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

ANKZF1 links:

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ACMG classification

Classification was made for transcript

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

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

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:

AN:

152204

Hom.:

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.53

M_CAP

Benign

0.0058

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.36

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.59

REVEL

Benign

0.016

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.29

Vest4

0.22

MutPred

0.11

Loss of solvent accessibility (P = 0.0217)

MVP

0.44

MPC

0.14

ClinPred

0.10

GERP RS

3.5

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.35

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over