17-56353933-A-G

Variant names:

• chr17-56353933-A-G
• NM_001370326.1:c.488A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370326.1(ANKFN1):​c.488A>G​(p.Asp163Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D163E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKFN1 NM_001370326.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

ANKFN1 (HGNC:26766): (ankyrin repeat and fibronectin type III domain containing 1) Predicted to be involved in establishment of mitotic spindle orientation and regulation of establishment of bipolar cell polarity. Predicted to act upstream of or within behavioral fear response; equilibrioception; and locomotor rhythm. Predicted to be active in spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKFN1	NM_001370326.1	c.488A>G	p.Asp163Gly	missense_variant	Exon 6 of 21	ENST00000682825.1	NP_001357255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000682825.1	c.488A>G	p.Asp163Gly	missense_variant	Exon 6 of 21		NM_001370326.1	ENSP00000507365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.497A>G (p.D166G) alteration is located in exon 5 (coding exon 5) of the ANKFN1 gene. This alteration results from a A to G substitution at nucleotide position 497, causing the aspartic acid (D) at amino acid position 166 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	2.0	.;M;.
PhyloP100		9.3
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.8	.;D;.
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0060	.;D;.
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.93, 0.96
MutPred		0.41		.;Loss of stability (P = 0.0732);Loss of stability (P = 0.0732);
MVP		0.92
MPC		0.69
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

hg19: chr17-54431294;