17-56372707-G-T

Position:

• chr17-56372707-G-T

Variant summary

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

The NM_001370326.1(ANKFN1):​c.663G>T​(p.Arg221Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 0.839

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKFN1	NM_001370326.1	c.663G>T	p.Arg221Ser	missense_variant	7/21	ENST00000682825.1	NP_001357255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000682825.1	c.663G>T	p.Arg221Ser	missense_variant	7/21		NM_001370326.1	ENSP00000507365	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

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

May 09, 2023

The c.672G>T (p.R224S) alteration is located in exon 6 (coding exon 6) of the ANKFN1 gene. This alteration results from a G to T substitution at nucleotide position 672, causing the arginine (R) at amino acid position 224 to be replaced by a serine (S). 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	0.81
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.2	.;D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	.;D;.
Sift4G	Uncertain	0.0070	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.80, 0.91
MutPred		0.33		.;Gain of phosphorylation at R224 (P = 0.0392);Gain of phosphorylation at R224 (P = 0.0392);
MVP		0.77
MPC		0.51
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.55
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-54450068;