chr2-219230327-C-G

Variant names:

• chr2-219230327-C-G
• rs372243770
• NM_018089.3:c.70C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018089.3(ANKZF1):​c.70C>G​(p.Pro24Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: ANKZF1 NM_018089.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.221
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059838295).

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.70C>G	p.Pro24Ala	missense	Exon 2 of 14	NP_060559.2	Q9H8Y5
	ANKZF1	NM_001042410.2		c.70C>G	p.Pro24Ala	missense	Exon 2 of 14	NP_001035869.1	Q9H8Y5
	ANKZF1	NM_001282792.2		c.-267+427C>G		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.70C>G	p.Pro24Ala	missense	Exon 2 of 14	ENSP00000321617.5	Q9H8Y5
	ANKZF1	ENST00000409849.5	TSL:1	c.-267+427C>G		intron	N/A	ENSP00000386815.1	B8ZZS4
	ANKZF1	ENST00000464763.5	TSL:1	n.218C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000125 AC: 31 AN: 248894 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000616 AC: 90 AN: 1461746 Hom.: 0 Cov.: 30 AF XY: 0.0000633 AC XY: 46 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000470 AC: 21 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111942

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.000262 AC: 4 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00143 AC: 3 AN: 2094

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.0000497 AC: 6

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.22
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.036
Sift	Benign	0.53	T
Sift4G	Benign	0.67	T
Polyphen		0.075	B
Vest4		0.29
MVP		0.56
MPC		0.11
ClinPred		0.059	T
GERP RS		2.7
PromoterAI		0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.17
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372243770; hg19: chr2-220095049;