17-56350887-C-A

Variant names:

• chr17-56350887-C-A
• rs753771498
• NM_001370326.1:c.310C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370326.1(ANKFN1):​c.310C>A​(p.Leu104Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L104V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ANKFN1 NM_001370326.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23523286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370326.1. 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
	ANKFN1	NM_001370326.1	MANE Select	c.310C>A	p.Leu104Met	missense	Exon 5 of 21	NP_001357255.1	Q8N957-1
	ANKFN1	NM_001365758.1		c.106C>A	p.Leu36Met	missense	Exon 5 of 21	NP_001352687.1
	ANKFN1	NM_153228.3		c.319C>A	p.Leu107Met	missense	Exon 4 of 17	NP_694960.2	Q8N957-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKFN1	ENST00000682825.1	MANE Select	c.310C>A	p.Leu104Met	missense	Exon 5 of 21	ENSP00000507365.1	Q8N957-1
	ANKFN1	ENST00000653862.1		c.760C>A	p.Leu254Met	missense	Exon 6 of 22	ENSP00000499705.1	A0A590UK59
	ANKFN1	ENST00000635860.2	TSL:5	c.586C>A	p.Leu196Met	missense	Exon 7 of 23	ENSP00000489811.2	A0A1B0GTR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.070
Sift	Benign	0.048	D
Sift4G	Uncertain	0.047	D
Polyphen		0.98	D
Vest4		0.47
MutPred		0.23		Gain of helix (P = 0.0022)
MVP		0.73
MPC		0.48
ClinPred		0.88	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.65
Mutation Taster		=90/10	polymorphism

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

dbSNP: rs753771498; hg19: chr17-54428248;