17-56326309-C-A

Position:

• chr17-56326309-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370326.1(ANKFN1):​c.142C>A​(p.Gln48Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKFN1 NM_001370326.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10592905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKFN1	NM_001370326.1	c.142C>A	p.Gln48Lys	missense_variant	4/21	ENST00000682825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKFN1	ENST00000682825.1	c.142C>A	p.Gln48Lys	missense_variant	4/21		NM_001370326.1	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.151C>A (p.Q51K) alteration is located in exon 3 (coding exon 3) of the ANKFN1 gene. This alteration results from a C to A substitution at nucleotide position 151, causing the glutamine (Q) at amino acid position 51 to be replaced by a lysine (K). 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	Benign	0.076
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T;T;T;.
Eigen	Benign	-0.029
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;N;.;.
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.49	.;N;.;.
REVEL	Benign	0.058
Sift	Benign	0.50	.;T;.;.
Sift4G	Benign	0.31	.;T;T;T
Polyphen		0.0040	.;B;.;.
Vest4		0.54, 0.44
MutPred		0.14		.;Gain of ubiquitination at Q51 (P = 0.0054);Gain of ubiquitination at Q51 (P = 0.0054);.;
MVP		0.69
MPC		0.19
ClinPred		0.33	T
GERP RS		5.1
Varity_R		0.15
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs866640368; hg19: chr17-54403670; COSMIC: COSV59441189;